BioMed Research International: Neuroscience The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Serial Serum Leukocyte Apoptosis Levels as Predictors of Outcome in Acute Traumatic Brain Injury Thu, 17 Apr 2014 13:33:18 +0000 Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI). This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome. Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects. Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (), motor deficits (), GCS (), ISS (), WBC count (), late apoptosis in lymphocytes and monocytes on Day 1 ( and , resp.), subdural hemorrhage on initial brain CT (), neurosurgical intervention (), and acute posttraumatic seizure () were significant risk factors of outcome. Only motor deficits () and late apoptosis in monocytes on Day 1 () were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients. Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury. Hung-Chen Wang, Tzu-Ming Yang, Yu-Jun Lin, Wu-Fu Chen, Jih-Tsun Ho, Yu-Tsai Lin, Aij-Lie Kwan, and Cheng-Hsien Lu Copyright © 2014 Hung-Chen Wang et al. All rights reserved. The Multiple Silicone Tube Device, “Tubes within a Tube,” for Multiplication in Nerve Reconstruction Thu, 17 Apr 2014 07:05:51 +0000 Multiple nerve branches were created during the regeneration procedure after a nerve injury and such multiple branches are suggested to be used to control, for example, prosthesis with many degrees of freedom. Transected rat sciatic nerve stumps were inserted into a nine mm long silicone tube, which contained four, five mm long, smaller tubes, thus leaving a five mm gap for regenerating nerve fibers. Six weeks later, several new nerve structures were formed not only in the four smaller tubes, but also in the spaces in-between. The 7–9 new continuous nerve structures, which were isolated as individual free nerves after removal of the tubes, were delineated by a perineurium and contained both myelinated and unmyelinated nerve fibers as well as blood vessels. Stimulation of the proximal nerve elicited contractions in distal muscles. Thin metal electrodes, inserted initially into the smaller tubes in some experiments, became embedded in the new nerve structures and when stimulated contractions of the distal muscles were observed. The “tubes within a tube” technique, creating multiple new nerves from a single “mother” nerve, can be used to record multiple signals for prosthetic device control or as sources for supply of multiple denervated targets. Fredrik Johansson and Lars B. Dahlin Copyright © 2014 Fredrik Johansson and Lars B. Dahlin. All rights reserved. Ghostman: Augmented Reality Application for Telerehabilitation and Remote Instruction of a Novel Motor Skill Tue, 15 Apr 2014 14:00:33 +0000 This paper describes a pilot study using a prototype telerehabilitation system (Ghostman). Ghostman is a visual augmentation system designed to allow a physical therapist and patient to inhabit each other’s viewpoint in an augmented real-world environment. This allows the therapist to deliver instruction remotely and observe performance of a motor skill through the patient’s point of view. In a pilot study, we investigated the efficacy of Ghostman by using it to teach participants to use chopsticks. Participants were randomized to a single training session, receiving either Ghostman or face-to-face instructions by the same skilled instructor. Learning was assessed by measuring retention of skills at 24-hour and 7-day post instruction. As hypothesised, there were no differences in reduction of error or time to completion between participants using Ghostman compared to those receiving face-to-face instruction. These initial results in a healthy population are promising and demonstrate the potential application of this technology to patients requiring learning or relearning of motor skills as may be required following a stroke or brain injury. Winyu Chinthammit, Troy Merritt, Scott Pedersen, Andrew Williams, Denis Visentin, Robert Rowe, and Thomas Furness Copyright © 2014 Winyu Chinthammit et al. All rights reserved. Sex Differences of Uncinate Fasciculus Structural Connectivity in Individuals with Conduct Disorder Mon, 14 Apr 2014 12:17:18 +0000 Conduct disorder (CD) is one of the most common behavior disorders in adolescents, such as impulsivity, aggression, and running from school. Males are more likely to develop CD than females, and two previous diffusion tensor imaging (DTI) studies have demonstrated abnormal microstructural integrity in the uncinate fasciculus (UF) in boys with CD compared to a healthy control group. However, little is known about changes in the UF in females with CD. In this study, the UF was illustrated by tractography; then, the fractional anisotropy (FA), axial diffusivity, mean diffusion, radial diffusivity (RD), and the length and number of the UF fiber bundles were compared between male and female patients with CD and between female patients with CD and female healthy controls, as well as between males with CD and healthy males. We found that males with CD showed significantly higher FA of the bilateral UF and significantly lower RD of the left UF when comparing with females with CD. Meanwhile, significantly higher FA and lower RD of the bilateral UF were also found in boys with CD relative to the male healthy controls. Our results replicated previous reports that the microstructural integrity of the UF was abnormal in boys with CD. Additionally, our results demonstrated significant gender effects on the UF of patients with CD, which may indicate why boys have higher rates of conduct problems than girls. Jibiao Zhang, Junling Gao, Huqing Shi, Bingsheng Huang, Xiang Wang, Weijun Situ, Weixiong Cai, Jinyao Yi, Xiongzhao Zhu, and Shuqiao Yao Copyright © 2014 Jibiao Zhang et al. All rights reserved. The Association between Serological Biomarkers and Primary Sjogren’s Syndrome Associated with Peripheral Polyneuropathy Sun, 13 Apr 2014 13:20:20 +0000 Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy of Sjogren’s syndrome (SJS) patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating autoantibodies levels in SJS patients with peripheral neuropathy. Methods. Two hundred and fifty serological positive (either anti-Ro or anti-La positive) SJS patients’ data were collected retrospectively. The titers of autoantibodies, electrophysiology reports, and clinical manifestation were reviewed. Results. The prevalence rate of peripheral neuropathy is 7.2% in our study. Regarding classification of peripheral neuropathy, 12 had mixed sensorimotor polyneuropathy, six had cranial neuropathy. After stepwise logistic regression analysis, anti-β2 glycoprotein I (aβ2GP I) and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) were significantly associated with peripheral neuropathy in serology positive SJS (, , resp.). Conclusion. The occurrence of peripheral neuropathy among SJS patients is not frequent and easily overlooked. Our study demonstrated that aβ2GP I and p-ANCA levels may imply the danger of the occurrence of neuropathy in SJS patients, and they can be considered a biomarker that should be added to the panel of conventional autoantibody in SJS patients. Che-Wei Hsu, Yu-Jih Su, Wen-Neng Chang, Nai-Wen Tsai, Wen-Chan Chiu, Ben-Chung Cheng, Chih-Min Su, Chi-Ren Huang, Ya-Ting Chang, and Cheng-Hsien Lu Copyright © 2014 Che-Wei Hsu et al. All rights reserved. Immune Responses in Parkinson’s Disease: Interplay between Central and Peripheral Immune Systems Sun, 13 Apr 2014 13:07:40 +0000 The etiology of Parkinson’s disease (PD) is complex and most likely involves numerous environmental and heritable risk factors. Recent studies establish that central and peripheral inflammation occurs in the prodromal stage of the disease and sustains disease progression. Aging, heritable risk factors, or environmental exposures may contribute to the initiation of central or peripheral inflammation. One emerging hypothesis is that inflammation plays a critical role in PD neuropathology. Increasing evidence suggest that activation of the peripheral immune system exacerbates the discordant central inflammatory response and synergistically drives neurodegeneration. We provide an overview of current knowledge on the temporal profile of central and peripheral immune responses in PD and discuss the potential synergistic effects of the central and peripheral inflammation in disease development. The understanding of the nature of the chronic inflammation in disease progression and the possible risk factors that contribute to altered central and peripheral immune responses will offer mechanistic insights into PD etiology and pathology and benefit the development of effective tailored therapeutics for human PD. Xiaomin Su and Howard J. Federoff Copyright © 2014 Xiaomin Su and Howard J. Federoff. All rights reserved. Progesterone and Mental Rotation Task: Is There Any Effect? Thu, 10 Apr 2014 14:10:49 +0000 Mental rotation task (MRT) incorporates elements of spatial abilities, important in many professions, with people of both genders involved. Importantly, these are the areas where spatial tasks might be performed for long time periods; thus adverse effects of mental fatigue are highly unwanted. Substantial variation of MRT performance in relation to estrogen levels has been observed in many studies, whereas the role of progesterone remains elusive. Here we aimed to elucidate the effect of progesterone level on the long-duration (1.5 hours) performance of MRT. We included three groups of subjects: a group of males as a control, a group of females in their follicular phase (low progesterone) and a group of females in their luteal phase (high progesterone), MRT accuracy and response time, subjective fatigue ratings and cardiovascular measures together with 17β-estradiol and progesterone concentrations were analyzed. We found that subjective ratings of fatigue increased, performance accuracy increased, and mean response times decreased during the task in all groups. Females in luteal phase were significantly slower not only than men, but also than females in their follicular phase. An increase in subjective fatigue ratings was positively related to progesterone level—at higher progesterone levels, females felt more tired. Donatas Noreika, Inga Griškova-Bulanova, Aidas Alaburda, Mindaugas Baranauskas, and Ramunė Grikšienė Copyright © 2014 Donatas Noreika et al. All rights reserved. The Combination of Carmustine Wafers and Fotemustine in Recurrent Glioblastoma Patients: A Monoinstitutional Experience Wed, 09 Apr 2014 14:01:34 +0000 Background. To date, there is no standard treatment for recurrent glioblastoma. We analyzed the feasibility of second surgery plus carmustine wafers followed by intravenous fotemustine. Methods. Retrospectively, we analyzed patients with recurrent glioblastoma treated with this multimodal strategy. Results. Twenty-four patients were analyzed. The median age was 53.6; all patients had KPS between 90 and 100; 19 patients (79%) performed a gross total resection > 98% and 5 (21%) a gross total resection > 90%. The median progression-free survival from second surgery was 6 months (95% CI 3.9–8.05) and the median OS was 14 months (95% CI 11.1–16.8 months). Toxicity was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia. Conclusion. This multimodal strategy may be feasible in patients with recurrent glioblastoma, in particular, for patients in good clinical conditions. Giuseppe Lombardi, Alessandro Della Puppa, Fable Zustovich, Ardi Pambuku, Patrizia Farina, Pasquale Fiduccia, Anna Roma, and Vittorina Zagonel Copyright © 2014 Giuseppe Lombardi et al. All rights reserved. Microparticles: A New Perspective in Central Nervous System Disorders Wed, 09 Apr 2014 13:53:32 +0000 Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer’s disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS. Stephanie M. Schindler, Jonathan P. Little, and Andis Klegeris Copyright © 2014 Stephanie M. Schindler et al. All rights reserved. 5-Aminolevulinic Acid Fluorescence in High Grade Glioma Surgery: Surgical Outcome, Intraoperative Findings, and Fluorescence Patterns Tue, 08 Apr 2014 00:00:00 +0000 Background. 5-Aminolevulinic acid (5-ALA) fluorescence is a validated technique for resection of high grade gliomas (HGG); the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Methods. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection % and %. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO). Results. 94 patients were finally enrolled. Overall % and % was achieved in 93% and 100% of patients. Extent of resection was dependent on tumor location, tumor grade , and tumor size . In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57%) and recurrent (60%) tumors. Conclusions. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings. Alessandro Della Puppa, Pietro Ciccarino, Giuseppe Lombardi, Giuseppe Rolma, Diego Cecchin, and Marta Rossetto Copyright © 2014 Alessandro Della Puppa et al. All rights reserved. Pu-Erh Tea Extract Induces the Degradation of FET Family Proteins Involved in the Pathogenesis of Amyotrophic Lateral Sclerosis Mon, 07 Apr 2014 09:19:09 +0000 FET family proteins consist of fused in sarcoma/translocated in liposarcoma (FUS/TLS), Ewing's sarcoma (EWS), and TATA-binding protein-associated factor 15 (TAF15). Mutations in the copper/zinc superoxide dismutase (SOD1), TAR DNA-binding protein 43 (TDP-43), and FET family proteins are associated with the development of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. There is currently no cure for this disease and few effective treatments are available. Epidemiological studies indicate that the consumption of tea is associated with a reduced risk of developing neurodegenerative diseases. The results of this study revealed that components of a pu-erh tea extract (PTE) interacted with FET family proteins but not with TDP-43 or SOD1. PTE induced the degradation of FET family proteins but had no effects on TDP-43 or SOD1. The most frequently occurring ALS-linked FUS/TLS mutant protein, R521C FUS/TLS, was also degraded in the presence of PTE. Furthermore, ammonium chloride, a lysosome inhibitor, but not lactacystin, a proteasome inhibitor, reduced the degradation of FUS/TLS protein by PTE. PTE significantly reduced the incorporation of R521C FUS/TLS into stress granules under stress conditions. These findings suggest that PTE may have beneficial health effects, including preventing the onset of FET family protein-associated neurodegenerative diseases and delaying the progression of ALS by inhibiting the cytoplasmic aggregation of FET family proteins. Yang Yu, Shuhei Hayashi, Xianbin Cai, Chongye Fang, Wei Shi, Hiroko Tsutsui, and Jun Sheng Copyright © 2014 Yang Yu et al. All rights reserved. CGP 35348, GABAB Receptor Antagonist, Has a Potential to Improve Neuromuscular Coordination and Spatial Learning in Albino Mouse following Neonatal Brain Damage Sun, 06 Apr 2014 13:05:28 +0000 To study the effect of CGP 35348 on learning and memory in albino mice following hypoxia ischemia insult, 10 days old albino mice were subjected to right common carotid artery ligation followed by 8% hypoxia for 25 minutes. Following brain damage, mice were fed on normal rodent diet till they were 13 week old. At this time point, mice were divided into two groups. Group 1 received saline and group 2 intrapertoneally CGP 35348 (1 mg/mL solvent/Kg body weight) for 12 days. A battery of tests used to assess long term neurofunction (Morris water maze, Rota rod and open field) along with brain infarct measurement. Overall CGP 35348 has improved the motor function in male and female albino mice but effects were more pronounced in female albino mice. In open field, CGP 35348 treated female albino mice had demonstrated poor exploratory behavior. During Morris water maze test, gender specific effects were observed as CGP 35348 had improved spatial learning and memory and swimming speed in male albino mice but had no effect in female albino mice following hypoxia ischemia encephalopathy (HIE). We concluded that GABAB receptor antagonists CGP 35348 can be used to improve gender based spatial memory. Q. Gillani, M. Ali, and F. Iqbal Copyright © 2014 Q. Gillani et al. All rights reserved. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury Thu, 03 Apr 2014 13:04:13 +0000 The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI. Wei-Ming Lin, Meng-Hsiang Chen, Hung-Chen Wang, Cheng-Hsien Lu, Pei-Chin Chen, Hsiu-Ling Chen, Nai-Wen Tsai, Yu-Jih Su, Shau-Hsuan Li, Chia-Te Kung, Tsui-Min Chiu, Hsu-Huei Weng, and Wei-Che Lin Copyright © 2014 Wei-Ming Lin et al. All rights reserved. Involvement of Endocytosis and Alternative Splicing in the Formation of the Pathological Process in the Early Stages of Parkinson’s Disease Thu, 03 Apr 2014 12:28:23 +0000 Parkinson’s disease (PD) is the one of most widespread neurodegenerative pathologies. Because of the impossibility of studying the endogenous processes that occur in the brain of patients with PD in the presymptomatic stage, the mechanisms that trigger the disease remain unknown. Thus, the identification of the processes that play an important role in the early stages of the disease in these patients is extremely difficult. In this context, we performed a whole-transcriptome analysis of the peripheral blood of untreated patients with stage 1 PD (Hoehn-Yahr scale). We demonstrated a significant change in the levels of transcripts included in the large groups of processes associated with the functioning of the immune system and cellular transport. Moreover, a significant change in the splicing of genes involved in cellular-transport processes was shown in our study. Anelya Kh. Alieva, Maria I. Shadrina, Elena V. Filatova, Aleksey V. Karabanov, Sergey N. Illarioshkin, Svetlana A. Limborska, and Petr A. Slominsky Copyright © 2014 Anelya Kh. Alieva et al. All rights reserved. Facing Contrast-Enhancing Gliomas: Perfusion MRI in Grade III and Grade IV Gliomas according to Tumor Area Thu, 03 Apr 2014 08:11:46 +0000 Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV), calculated with Dynamic Susceptibility Contrast (DSC) Perfusion-Weighted Imaging (PWI), allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI) approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV). Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp.), the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78, ). In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading. Anna Luisa Di Stefano, Niels Bergsland, Giulia Berzero, Lisa Farina, Elisa Rognone, Matteo Gastaldi, Domenico Aquino, Alessandro Frati, Francesco Tomasello, Mauro Ceroni, Enrico Marchioni, and Stefano Bastianello Copyright © 2014 Anna Luisa Di Stefano et al. All rights reserved. Dissociable Self Effects for Emotion Regulation: A Study of Chinese Major Depressive Outpatients Thu, 03 Apr 2014 06:37:31 +0000 Reappraisal is an adaptive emotion regulation strategy while the role of self-perspective in reappraisal process of depressed patients is largely unknown in terms of goals (valence/arousal) and tactics (detachment/immersion). In this study, 12 depressed individuals and 15 controls were scanned with MRI during which they either attend naturally to emotional stimuli, or adopt detachment/immersion strategy. Behaviorally, no group differences in self-reported emotion regulation effectiveness were found. In addition, we observed that (1) patients were less able to downregulate amygdala activation with recruitment of more dorsal lateral prefrontal cortex (dlPFC) when adopting detachment strategy regardless of valence, and this preserved ability to regulate emotion was inversely associated with severity of symptoms; (2) patients had deficits in upregulating amygdala activation when adopting immersion strategy, with less inferior frontal gyrus (IFG) activation and strengthening coupling of dlPFC and ventral medial prefrontal cortex (vmPFC) with amygdala; (3) comparison between groups yielded that patients showed stronger vmPFC activation under either self-detached or self-immersed condition. In conclusion, impaired modulatory effects of amygdala in depressed patients are compensated with strengthening cognitive control resources, with dissociable effects for different self-perspectives in reappraisal. These results may help clarify the role of self-perspective underlying reappraisal in major depression. Xiaoxia Wang, Zhengzhi Feng, Daiquan Zhou, Xu Lei, Tongquan Liao, Li Zhang, Bing Ji, and Jing Li Copyright © 2014 Xiaoxia Wang et al. All rights reserved. An ANOCEF Genomic and Transcriptomic Microarray Study of the Response to Irinotecan and Bevacizumab in Recurrent Glioblastomas Wed, 02 Apr 2014 13:26:47 +0000 Background. We performed a retrospective study to assess whether the initial molecular characteristics of glioblastomas (GBMs) were associated with the response to the bevacizumab/irinotecan chemotherapy regimen given at recurrence. Results. Comparison of the genomic and gene expression profiles of the responders () and nonresponders () demonstrated only slight differences and could not identify any robust biomarkers associated with the response. In contrast, a significant association was observed between GBMs molecular subtypes and response rates. GBMs assigned to molecular subtype IGS-18 and to classical subtype had a lower response rate than those assigned to other subtypes. In an independent series of 33 patients, neither EGFR amplification nor CDKN2A deletion (which are frequent in IGS-18 and classical GBMs) was significantly associated with the response rate, suggesting that these two alterations are unlikely to explain the lower response rate of these GBMs molecular subtypes. Conclusion. Despite its limited sample size, the present study suggests that comparing the initial molecular profiles of responders and nonresponders might not be an effective strategy to identify biomarkers of the response to bevacizumab given at recurrence. Yet it suggests that the response rate might differ among GBMs molecular subtypes. Julien Laffaire, Anna Luisa Di Stefano, Olivier Chinot, Ahmed Idbaih, Jaime Gallego Perez-Larraya, Yannick Marie, Nadia Vintonenko, Blandine Boisselier, Patrizia Farina, Jean-Yves Delattre, Dominique Figarella-Branger, Jérôme Honnorat, Marc Sanson, and François Ducray Copyright © 2014 Julien Laffaire et al. All rights reserved. An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab Mon, 31 Mar 2014 10:12:39 +0000 Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas. Giuseppe Lombardi, Patrizia Farina, Alessandro Della Puppa, Diego Cecchin, Ardi Pambuku, Luisa Bellu, and Vittorina Zagonel Copyright © 2014 Giuseppe Lombardi et al. All rights reserved. Assessing Response Using -MIBI Early after Interstitial Chemotherapy with Carmustine-Loaded Polymers in Glioblastoma Multiforme: Preliminary Results Thu, 27 Mar 2014 16:32:52 +0000 Introduction. Early signs of response after applying wafers of carmustine-loaded polymers (gliadel) are difficult to assess with imaging because of time-related imaging changes. -sestamibi (MIBI) brain single-photon emission tomography (SPET) has reportedly been used to reveal areas of cellularity distinguishing recurrent neoplasm from radionecrosis. Our aim was to explore the role of MIBI SPET in assessing response soon after gliadel application in glioblastoma multiforme (GBM). Methods. We retrospectively reviewed the charts on 28 consecutive patients with a radiological diagnosis of GBM who underwent MIBI SPET/CT before surgery (with intracavitary gliadel placement in 17 patients), soon after surgery, and at 4 months. The area of uptake was selected using a volume of interest that was then mirrored contralaterally to obtain a semiquantitative ratio. Results. After adjusting for ratio at the baseline, the effect of treatment (gliadel versus non-gliadel) was not statistically significant. Soon after surgery, however, 100% of patients treated with gliadel had a decreased ratio, as opposed to 62.5% of patients in the non-gliadel group . The difference between ratios of patients with radical versus partial resection reached statistical significance by a small margin . Conclusions. These data seem to suggest that the MIBI ratio could be a valuable tool for monitoring the effect of gliadel early after surgery. D. Cecchin, I. Schiorlin, A. Della Puppa, G. Lombardi, P. Zucchetta, V. Bodanza, M. P. Gardiman, G. Rolma, A. C. Frigo, and F. Bui Copyright © 2014 D. Cecchin et al. All rights reserved. Peripheral Leukocyte Apoptosis in Patients with Parkinsonism: Correlation with Clinical Characteristics and Neuroimaging Findings Wed, 26 Mar 2014 00:00:00 +0000 Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson’s disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using -TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression. Wei-Che Lin, Nai-Wen Tsai, Yung-Cheng Huang, Kuei-Yueh Cheng, Hsiu-Ling Chen, Shau-Hsuan Li, Chia-Te Kung, Yu-Jih Su, Wei-Ming Lin, Meng-Hsiang Chen, Tsui-Min Chiu, I-Hsiao Yang, and Cheng-Hsien Lu Copyright © 2014 Wei-Che Lin et al. All rights reserved. Does rTMS Alter Neurocognitive Functioning in Patients with Panic Disorder/Agoraphobia? An fNIRS-Based Investigation of Prefrontal Activation during a Cognitive Task and Its Modulation via Sham-Controlled rTMS Tue, 18 Mar 2014 00:00:00 +0000 Objectives. Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Conclusion. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed. Saskia Deppermann, Nadja Vennewald, Julia Diemer, Stephanie Sickinger, Florian B. Haeussinger, Swantje Notzon, Inga Laeger, Volker Arolt, Ann-Christine Ehlis, Peter Zwanzger, and Andreas J. Fallgatter Copyright © 2014 Saskia Deppermann et al. All rights reserved. Abnormal Early Gamma Responses to Emotional Faces Differentiate Unipolar from Bipolar Disorder Patients Thu, 13 Mar 2014 12:39:52 +0000 This study investigates the cortical abnormalities of early emotion perception in patients with major depressive disorder (MDD) and bipolar disorder (BD) using gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and twenty-four normal controls were enrolled and their event-related magnetoencephalographic responses were recorded during implicit emotional tasks. Our results demonstrated abnormal gamma activity within 100 ms in the emotion-related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and superior temporal pole) in the MDD patients, suggesting that these patients may have dysfunctions or negativity biases in perceptual binding of emotional features at very early stage. Decreased left superior medial frontal cortex (smFC) responses to happy faces in the MDD patients were correlated with their serious level of depression symptoms, indicating that decreased smFC activity perhaps underlies irregular positive emotion processing in depressed patients. In the BD patients, we showed abnormal activation in visual regions (inferior/middle occipital and middle temporal cortices) which responded to emotional faces within 100 ms, supporting that the BD patients may hyperactively respond to emotional features in perceptual binding. The discriminant function of gamma activation in the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral cortex accurately classified 89.6% of patients as unipolar/bipolar disorders. T. Y. Liu, Y. S. Chen, T. P. Su, J. C. Hsieh, and L. F. Chen Copyright © 2014 T. Y. Liu et al. All rights reserved. Fear Processing in Dental Phobia during Crossmodal Symptom Provocation: An fMRI Study Tue, 11 Mar 2014 11:42:01 +0000 While previous studies successfully identified the core neural substrates of the animal subtype of specific phobia, only few and inconsistent research is available for dental phobia. These findings might partly relate to the fact that, typically, visual stimuli were employed. The current study aimed to investigate the influence of stimulus modality on neural fear processing in dental phobia. Thirteen dental phobics (DP) and thirteen healthy controls (HC) attended a block-design functional magnetic resonance imaging (fMRI) symptom provocation paradigm encompassing both visual and auditory stimuli. Drill sounds and matched neutral sinus tones served as auditory stimuli and dentist scenes and matched neutral videos as visual stimuli. Group comparisons showed increased activation in the insula, anterior cingulate cortex, orbitofrontal cortex, and thalamus in DP compared to HC during auditory but not visual stimulation. On the contrary, no differential autonomic reactions were observed in DP. Present results are largely comparable to brain areas identified in animal phobia, but also point towards a potential downregulation of autonomic outflow by neural fear circuits in this disorder. Findings enlarge our knowledge about neural correlates of dental phobia and may help to understand the neural underpinnings of the clinical and physiological characteristics of the disorder. Kevin Hilbert, Ricarda Evens, Nina Isabel Maslowski, Hans-Ulrich Wittchen, and Ulrike Lueken Copyright © 2014 Kevin Hilbert et al. All rights reserved. A Preliminary Study of the Influence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder Thu, 06 Mar 2014 09:56:18 +0000 Background. Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Methods. Adults with MDD () and controls (HC; ) underwent magnetic resonance imaging. Twenty patients had MDD onset 24 years of age (pediatric onset) and 16 had onset 25 years of age (adult onset). The MDD group was also subdivided into those with () and without () physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Results. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. Conclusions. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation. Natalia Jaworska, Frank P. MacMaster, Ismael Gaxiola, Filomeno Cortese, Bradley Goodyear, and Rajamannar Ramasubbu Copyright © 2014 Natalia Jaworska et al. All rights reserved. Controversial Issues in Kyphoplasty and Vertebroplasty in Osteoporotic Vertebral Fractures Tue, 04 Mar 2014 13:05:44 +0000 Kyphoplasty (KP) and vertebroplasty (VP) have been successfully employed for many years for the treatment of osteoporotic vertebral fractures. The purpose of this review is to resolve the controversial issues raised by the two randomized trials that claimed no difference between VP and SHAM procedure. In particular we compare nonsurgical management (NSM) and KP and VP, in terms of clinical parameters (pain, disability, quality of life, and new fractures), cost-effectiveness, radiological variables (kyphosis correction and vertebral height restoration), and VP versus KP for cement extravasation and complications profile. Cement types and optimal filling are analyzed and technological innovations are presented. Finally unipedicular/bipedicular techniques are compared. Conclusion. VP and KP are superior to NSM in clinical and radiological parameters and probably more cost-effective. KP is superior to VP in sagittal balance improvement and cement leaking. Complications are rare but serious adverse events have been described, so caution should be exerted. Unilateral procedures should be pursued whenever feasible. Upcoming randomized trials (CEEP, OSTEO-6, STIC-2, and VERTOS IV) will provide the missing link. Ioannis D. Papanastassiou, Andreas Filis, Maria A. Gerochristou, and Frank D. Vrionis Copyright © 2014 Ioannis D. Papanastassiou et al. All rights reserved. Reduced Amygdala Volume Is Associated with Deficits in Inhibitory Control: A Voxel- and Surface-Based Morphometric Analysis of Comorbid PTSD/Mild TBI Mon, 03 Mar 2014 16:53:13 +0000 A significant portion of previously deployed combat Veterans from Operation Enduring Freedom and Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) are affected by comorbid posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Despite this fact, neuroimaging studies investigating the neural correlates of cognitive dysfunction within this population are almost nonexistent, with the exception of research examining the neural correlates of diagnostic PTSD or TBI. The current study used both voxel-based and surface-based morphometry to determine whether comorbid PTSD/mTBI is characterized by altered brain structure in the same regions as observed in singular diagnostic PTSD or TBI. Furthermore, we assessed whether alterations in brain structures in these regions were associated with behavioral measures related to inhibitory control, as assessed by the Go/No-go task, self-reports of impulsivity, and/or PTSD or mTBI symptoms. Results indicate volumetric reductions in the bilateral anterior amygdala in our comorbid PTSD/mTBI sample as compared to a control sample of OEF/OIF Veterans with no history of mTBI and/or PTSD. Moreover, increased volume reduction in the amygdala predicted poorer inhibitory control as measured by performance on the Go/No-go task, increased self-reported impulsivity, and greater symptoms associated with PTSD. These findings suggest that alterations in brain anatomy in OEF/OIF/OND Veterans with comorbid PTSD/mTBI are associated with both cognitive deficits and trauma symptoms related to PTSD. B. E. Depue, J. H. Olson-Madden, H. R. Smolker, M. Rajamani, L. A. Brenner, and M. T. Banich Copyright © 2014 B. E. Depue et al. All rights reserved. Diffusion Tensor Imaging Studies on Chinese Patients with Social Anxiety Disorder Mon, 03 Mar 2014 16:50:44 +0000 The aim of this study was to explore white-matter disruption in social anxiety disorder (SAD) patients by using diffusion tensor imaging (DTI) and to investigate the relationship between cerebral abnormalities and the severity of the symptoms. Eighteen SAD patients and age- and gender-matched healthy controls were recruited. DTI scans were performed to measure fractional anisotropy (FA) and apparent diffusion coefficient (ADC) for each subject. We used voxel-based analysis to determine the differences of FA and ADC values between the two groups with two-sample -tests. The SAD patient showed significantly decreased FA values in the white matter of the left insula, left inferior frontal gyrus, left middle temporal gyrus, and left inferior parietal gyrus and increased ADC values in the left insula, bilateral inferior frontal gyrus, bilateral middle temporal gyrus, and left inferior parietal gyrus. In SAD patients, we observed a significant negative correlation between FA values in the left insula and the total LSAS scores and a positive correlation between the ADC values in the left inferior frontal gyrus and the total LSAS scores. Above results suggested that white-matter microstructural changes might contribute to the neuropathology of SAD. Changjian Qiu, Chunyan Zhu, Jingna Zhang, Xiaojing Nie, Yuan Feng, Yajing Meng, Ruizhi Wu, Xiaoqi Huang, Wei Zhang, and Qiyong Gong Copyright © 2014 Changjian Qiu et al. All rights reserved. Designs and Techniques That Improve the Pullout Strength of Pedicle Screws in Osteoporotic Vertebrae: Current Status Mon, 03 Mar 2014 06:52:23 +0000 Osteoporosis is a medical condition affecting men and women of different age groups and populations. The compromised bone quality caused by this disease represents an important challenge when a surgical procedure (e.g., spinal fusion) is needed after failure of conservative treatments. Different pedicle screw designs and instrumentation techniques have been explored to enhance spinal device fixation in bone of compromised quality. These include alterations of screw thread design, optimization of pilot hole size for non-self-tapping screws, modification of the implant’s trajectory, and bone cement augmentation. While the true benefits and limitations of any procedure may not be realized until they are observed in a clinical setting, axial pullout tests, due in large part to their reproducibility and ease of execution, are commonly used to estimate the device’s effectiveness by quantifying the change in force required to remove the screw from the body. The objective of this investigation is to provide an overview of the different pedicle screw designs and the associated surgical techniques either currently utilized or proposed to improve pullout strength in osteoporotic patients. Mechanical comparisons as well as potential advantages and disadvantages of each consideration are provided herein. Thomas M. Shea, Jake Laun, Sabrina A. Gonzalez-Blohm, James J. Doulgeris, William E. Lee III, Kamran Aghayev, and Frank D. Vrionis Copyright © 2014 Thomas M. Shea et al. All rights reserved. Surface-Based Regional Homogeneity in First-Episode, Drug-Naïve Major Depression: A Resting-State fMRI Study Tue, 25 Feb 2014 11:30:15 +0000 Background. Previous volume-based regional homogeneity (ReHo) studies neglected the intersubject variability in cortical folding patterns. Recently, surface-based ReHo was developed to reduce the intersubject variability and to increase statistical power. The present study used this novel surface-based ReHo approach to explore the brain functional activity differences between first-episode, drug-naïve MDD patients and healthy controls. Methods. Thirty-three first-episode, drug-naïve MDD patients and 32 healthy controls participated in structural and resting-state fMRI scans. MDD patients were rated with a 17-item Hamilton Rating Scale for Depression prior to the scan. Results. In comparison with the healthy controls, MDD patients showed reduced surface-based ReHo in the left insula. There was no increase in surface-based ReHo in MDD patients. The surface-based ReHo value in the left insula was not significantly correlated with the clinical information or the depressive scores in the MDD group. Conclusions. The decreased surface-based ReHo in the left insula in MDD may lead to the abnormal top-down cortical-limbic regulation of emotional and cognitive information. The surface-based ReHo may be a useful index to explore the pathophysiological mechanism of MDD. Hui-Jie Li, Xiao-Hua Cao, Xing-Ting Zhu, Ai-Xia Zhang, Xiao-Hui Hou, Yong Xu, Xi-Nian Zuo, and Ke-Rang Zhang Copyright © 2014 Hui-Jie Li et al. All rights reserved. Percutaneous Cement-Augmented Screws Fixation in the Fractures of the Aging Spine: Is It the Solution? Thu, 20 Feb 2014 12:50:15 +0000 Introduction. Management of elderly patients with thoracolumbar fractures is still challenging due to frequent osteoporosis and risk of screws pull-out. The aim of this study was to evaluate results of a percutaneous-only procedure to treat these fragile patients using cement-augmented screws. Methods. 12 patients diagnosed with a thoracolumbar fracture associated with an important loss of bone stock were included in this prospective study. Surgical procedure included systematically a percutaneous osteosynthesis using cemented fenestrated screws. When necessary, additional anterior support was performed using a kyphoplasty procedure. Clinical and radiographic evaluations were performed using CT scan. Results. On the whole series, 15 fractures were diagnosed and 96 cemented screws were inserted. The difference between the pre- and postoperative vertebral kyphosis was statistically significant (12.9° versus 4.4°, ). No extrapedicular screw was reported and one patient was diagnosed with a cement-related pulmonary embolism. During follow-up period, no infectious complications, implant failures, or pull-out screws were noticed. Discussion. Aging spine is becoming an increasing public health issue. Management of these patients requires specific attention due to the augmented risk of complications. Using percutaneous-only screws fixation with cemented screw provides satisfactory results. A rigorous technique is mandatory in order to achieve best outcomes. Sébastien Pesenti, Benjamin Blondel, Emilie Peltier, Tarek Adetchessi, Henry Dufour, and Stéphane Fuentes Copyright © 2014 Sébastien Pesenti et al. All rights reserved. Proton Pump Inhibition Increases Rapid Eye Movement Sleep in the Rat Wed, 19 Feb 2014 11:41:10 +0000 Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor “lansoprazole” on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg) were injected intraperitoneally in the same animal () and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was and , respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle) and 34.21% (from low dose). Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker “amiloride” (10 mg/kg; i.p.) () did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep. Munazah Fazal Qureshi and Sushil K. Jha Copyright © 2014 Munazah Fazal Qureshi and Sushil K. Jha. All rights reserved. Systematic Review on Surgical and Nonsurgical Treatment of Type II Odontoid Fractures in the Elderly Mon, 10 Feb 2014 09:25:45 +0000 Odontoid fractures type II according to Anderson and d’Alonzo are not uncommon in the elderly patients. Still, due to the paucity of evidence the published treatment guidelines are far from equivocal. This systematic review focuses on the published results of type II odontoid fracture treatment in the elderly with regard to survival, nonunion, and complications. After a systematic literature research 38 publications were included. A cumulative analysis of 1284 published cases found greater survival if elderly patients with odontoid fractures type II received surgical treatment (RR = 0.64). With regard to nonunion in 669 published cases primary posterior fusion had the best fusion results. The systematic literature review came to the following conclusions. (1) Surgical stabilisation of odontoid fractures type II improves survival in patients between 65 and 85 years of age compared to nonsurgical treatment. (2) Posterior atlantoaxial fusion for odontoid fractures type II in the elderly has the greatest bony union rate. (3) Odontoid nonunion is not associated with worse clinical or functional results in the elderly. (4) The complication rate of nonsurgical treatment is similar to the complication rate of surgical treatment of odontoid fractures type II in the elderly. Yohan Robinson, Anna-Lena Robinson, and Claes Olerud Copyright © 2014 Yohan Robinson et al. All rights reserved. Mesenchymal Stem Cells Expressing Brain-Derived Neurotrophic Factor Enhance Endogenous Neurogenesis in an Ischemic Stroke Model Wed, 05 Feb 2014 13:52:01 +0000 Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2′-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis. Chang Hyun Jeong, Seong Muk Kim, Jung Yeon Lim, Chung Heon Ryu, Jin Ae Jun, and Sin-Soo Jeun Copyright © 2014 Chang Hyun Jeong et al. All rights reserved. A Mushroom Extract Piwep from Phellinus igniarius Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Immune Cell Infiltration in the Spinal Cord Mon, 27 Jan 2014 07:25:49 +0000 The present study aimed to evaluate the therapeutic potential of a mushroom extract from Phellinus igniarius in an animal model of multiple sclerosis. The medicinal mushroom, Phellinus igniarius, contains biologically active compounds that modulate the human immune system. Experimental autoimmune encephalomyelitis (EAE) was induced by immunization with myelin oligodendrocyte glycoprotein (MOG 35–55) in C57BL/6 female mice. A water-ethanol extract of Phellinus igniarius (Piwep) was delivered intraperitoneally every other day for the entire experimental course. Three weeks after the initial immunization, demyelination and immune cell infiltration in the spinal cord were examined. Piwep injection profoundly decreased the daily incidence rate and clinical score of EAE. The Piwep-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, macrophages, and B cells in the spinal cord. Piwep reduced expression of vascular cell adhesion molecule-1 (VCAM-1) in the spinal cord and integrin- in the lymph node of EAE mice. Piwep also inhibited proliferation of lymphocytes and secretion of interferon- in the lymph node of EAE mice. The results suggest that a mushroom extract, Piwep, may have a high therapeutic potential for ameliorating multiple sclerosis progression. Lan Li, Guang Wu, Bo Young Choi, Bong Geom Jang, Jin Hee Kim, Gi Ho Sung, Jae Youl Cho, Sang Won Suh, and Hyoung Jin Park Copyright © 2014 Lan Li et al. All rights reserved. Stereotactic Radiosurgery with Neoadjuvant Embolization of Larger Arteriovenous Malformations: An Institutional Experience Wed, 22 Jan 2014 14:09:48 +0000 Objective. This study investigates the safety and efficacy of a multimodality approach combining staged endovascular embolizations with subsequent SRS for the management of larger AVMs. Methods. Ninety-five patients with larger AVMs were treated with staged endovascular embolization followed by SRS between 1996 and 2011. Results. The median volume of AVM in this series was 28 cm3 and 47 patients (48%) were Spetzler-Martin grade IV or V. Twenty-seven patients initially presented with hemorrhage. Sixty-one patients underwent multiple embolizations while a single SRS session was performed in 64 patients. The median follow-up after SRS session was 32 months (range 9–136 months). Overall procedural complications occurred in 14 patients. There were 13 minor neurologic complications and 1 major complication (due to embolization) while four patients had posttreatment hemorrhage. Thirty-eight patients (40%) were cured radiographically. The postradiosurgery actuarial rate of obliteration was 45% at 5 years, 56% at 7 years, and 63% at 10 years. In multivariate analysis, larger AVM size, deep venous drainage, and the increasing number of embolization/SRS sessions were negative predictors of obliteration. The number of embolizations correlated positively with the number of stereotactic radiosurgeries (). Conclusions. Multimodality endovascular and radiosurgical approach is an efficacious treatment strategy for large AVM. Richard Dalyai, Thana Theofanis, Robert M. Starke, Nohra Chalouhi, George Ghobrial, Pascal Jabbour, Aaron S. Dumont, L. Fernando Gonzalez, David S. Gordon, Robert H. Rosenwasser, and Stavropoula I. Tjoumakaris Copyright © 2014 Richard Dalyai et al. All rights reserved. Notch1 and 4 Signaling Responds to an Increasing Vascular Wall Shear Stress in a Rat Model of Arteriovenous Malformations Mon, 20 Jan 2014 12:09:29 +0000 Notch signaling is suggested to promote the development and maintenance of cerebral arteriovenous malformations (AVMs), and an increasing wall shear stress (WSS) contributes to AVM rupture. Little is known about whether WSS impacts Notch signaling, which is important for understanding the angiogenesis of AVMs. WSS was measured in arteriovenous fistulas (AVF) surgically created in 96 rats at different time points over a period of 84 days. The expression of Notch receptors 1 and 4 and their ligands, Delta1 and 4, Jagged1, and Notch downstream gene target Hes1 was quantified in “nidus” vessels. The interaction events between Notch receptors and their ligands were quantified using proximity ligation assay. There was a positive correlation between WSS and time (; ). The expression of Notch receptors and their ligands was upregulated following AVF formation. There was a positive correlation between time and the number of interactions between Notch receptors and their ligands aftre AVF formation (, ) and a positive correlation between WSS and the number of interactions between Notch receptors and their ligands (, ). In conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by activation of Notch signaling. Jian Tu, Yang Li, and Zhiqiang Hu Copyright © 2014 Jian Tu et al. All rights reserved. Neuroanatomical Classification in a Population-Based Sample of Psychotic Major Depression and Bipolar I Disorder with 1 Year of Diagnostic Stability Sun, 19 Jan 2014 13:55:13 +0000 The presence of psychotic features in the course of a depressive disorder is known to increase the risk for bipolarity, but the early identification of such cases remains challenging in clinical practice. In the present study, we evaluated the diagnostic performance of a neuroanatomical pattern classification method in the discrimination between psychotic major depressive disorder (MDD), bipolar I disorder (BD-I), and healthy controls (HC) using a homogenous sample of patients at an early course of their illness. Twenty-three cases of first-episode psychotic mania (BD-I) and 19 individuals with a first episode of psychotic MDD whose diagnosis remained stable during 1 year of followup underwent 1.5 T MRI at baseline. A previously validated multivariate classifier based on support vector machine (SVM) was employed and measures of diagnostic performance were obtained for the discrimination between each diagnostic group and subsamples of age- and gender-matched controls recruited in the same neighborhood of the patients. Based on T1-weighted images only, the SVM-classifier afforded poor discrimination in all 3 pairwise comparisons: BD-I versus HC; MDD versus HC; and BD-I versus MDD. Thus, at the population level and using structural MRI only, we failed to achieve good discrimination between BD-I, psychotic MDD, and HC in this proof of concept study. Mauricio H. Serpa, Yangming Ou, Maristela S. Schaufelberger, Jimit Doshi, Luiz K. Ferreira, Rodrigo Machado-Vieira, Paulo R. Menezes, Marcia Scazufca, Christos Davatzikos, Geraldo F. Busatto, and Marcus V. Zanetti Copyright © 2014 Mauricio H. Serpa et al. All rights reserved. Adverse Prognostic Factors and Optimal Intervention Time for Kyphoplasty/Vertebroplasty in Osteoporotic Fractures Sun, 19 Jan 2014 07:25:05 +0000 Introduction. While evidence supports the efficacy of vertebral augmentation (kyphoplasty and vertebroplasty) for the treatment of osteoporotic fractures, randomized trials disputed the value of vertebroplasty. The aim of this analysis is to determine the subset of patients that may not benefit from surgical intervention and find the optimal intervention time. Methods. 27 prospective multiple-arm studies with cohorts of more than 20 patients were included in this meta-analysis. We hereby report the results from the metaregression and subset analysis of those trials reporting on treatment of osteoporotic fractures with kyphoplasty and/or vertebroplasty. Results. Early intervention (first 7 weeks after fracture) yielded more pain relief. However, spontaneous recovery was encountered in hyperacute fractures (less than 2 weeks old). Patients suffering from thoracic fractures or severely deformed vertebrae tended to report inferior results. We also attempted to formulate a treatment algorithm. Conclusion. Intervention in the hyperacute period should not be pursued, while augmentation after 7 weeks yields less consistent results. In cases of thoracic fractures and significant vertebral collapse, surgeons or interventional radiologists may resort earlier to operation and be less conservative, although those parameters need to be addressed in future randomized trials. Ioannis D. Papanastassiou, Andreas Filis, Kamran Aghayev, Zinon T. Kokkalis, Maria A. Gerochristou, and Frank D. Vrionis Copyright © 2014 Ioannis D. Papanastassiou et al. All rights reserved. Continuous Selective Intra-Arterial Application of Nimodipine in Refractory Cerebral Vasospasm due to Aneurysmal Subarachnoid Hemorrhage Thu, 16 Jan 2014 07:18:02 +0000 Background. Cerebral vasospasm is one of the leading courses for disability in aneurysmal subarachnoid hemorrhage. Effective treatment of vasospasm is therefore one of the main priorities for these patients. We report about a case series of continuous intra-arterial infusion of the calcium channel antagonist nimodipine for 1–5 days on the intensive care unit. Methods. In thirty patients with aneurysmal subarachnoid hemorrhage and refractory vasospasm continuous infusion of nimodipine was started on the neurosurgical intensive care unit. The effect of nimodipine on brain perfusion, cerebral blood flow, brain tissue oxygenation, and blood flow velocity in cerebral arteries was monitored. Results. Based on Hunt & Hess grades on admission, 83% survived in a good clinical condition and 23% recovered without an apparent neurological deficit. Persistent ischemic areas were seen in 100% of patients with GOS 1–3 and in 69% of GOS 4-5 patients. Regional cerebral blood flow and computed tomography perfusion scanning showed adequate correlation with nimodipine application and angiographic vasospasm. Transcranial Doppler turned out to be unreliable with interexaminer variance and failure of detecting vasospasm or missing the improvement. Conclusion. Local continuous intra-arterial nimodipine treatment for refractory cerebral vasospasm after aSAH can be recommended as a low-risk treatment in addition to established endovascular therapies. Stephanie Ott, Sheila Jedlicka, Stefan Wolf, Mozes Peter, Christine Pudenz, Patrick Merker, Ludwig Schürer, and Christianto Benjamin Lumenta Copyright © 2014 Stephanie Ott et al. All rights reserved. Long-Term Effects of Postearthquake Distress on Brain Microstructural Changes Tue, 14 Jan 2014 14:16:10 +0000 Stressful events can have both short- and long-term effects on the brain. Our recent investigation identified short-term white matter integrity (WMI) changes in 30 subjects soon after the Japanese earthquake. Our findings suggested that lower WMI in the right anterior cingulum (Cg) was a pre-existing vulnerability factor and increased WMI in the left anterior Cg and uncinate fasciculus (Uf) after the earthquake was an acquired sign of postearthquake distress. However, the long-term effects on WMI remained unclear. Here, we examined the 1-year WMI changes in 25 subjects to clarify long-term effects on the WMI. We found differential FAs in the right anterior Cg, bilateral Uf, left superior longitudinal fasciculus (SLF), and left thalamus, suggesting that synaptic enhancement and shrinkage were long-term effects. Additionally, the correlation between psychological measures related to postearthquake distress and the degree of WMI alternation in the right anterior Cg and the left Uf led us to speculate that temporal WMI changes in some subjects with emotional distress occurred soon after the disaster. We hypothesized that dynamic WMI changes predict a better prognosis, whereas persistently lower WMI is a marker of cognitive dysfunction, implying the development of anxiety disorders. Atsushi Sekiguchi, Yuka Kotozaki, Motoaki Sugiura, Rui Nouchi, Hikaru Takeuchi, Sugiko Hanawa, Seishu Nakagawa, Carlos Makoto Miyauchi, Tsuyoshi Araki, Atsushi Sakuma, Yasuyuki Taki, and Ryuta Kawashima Copyright © 2014 Atsushi Sekiguchi et al. All rights reserved. Neurotoxicants Are in the Air: Convergence of Human, Animal, and In Vitro Studies on the Effects of Air Pollution on the Brain Sun, 12 Jan 2014 00:00:00 +0000 In addition to increased morbidity and mortality caused by respiratory and cardiovascular diseases, air pollution may also negatively affect the brain and contribute to central nervous system diseases. Air pollution is a mixture comprised of several components, of which ultrafine particulate matter (UFPM; <100 nm) is of much concern, as these particles can enter the circulation and distribute to most organs, including the brain. A major constituent of ambient UFPM is represented by traffic-related air pollution, mostly ascribed to diesel exhaust (DE). Human epidemiological studies and controlled animal studies have shown that exposure to air pollution may lead to neurotoxicity. In addition to a variety of behavioral abnormalities, two prominent effects caused by air pollution are oxidative stress and neuroinflammation, which are seen in both humans and animals and are confirmed by in vitro studies. Among factors which can affect neurotoxic outcomes, age is considered the most relevant. Human and animal studies suggest that air pollution (and DE) may cause developmental neurotoxicity and may contribute to the etiology of neurodevelopmental disorders, including autistic spectrum disorders. In addition, air pollution exposure has been associated with increased expression of markers of neurodegenerative disease pathologies. Lucio G. Costa, Toby B. Cole, Jacki Coburn, Yu-Chi Chang, Khoi Dao, and Pamela Roque Copyright © 2014 Lucio G. Costa et al. All rights reserved. Effects of Stress and MDMA on Hippocampal Gene Expression Thu, 09 Jan 2014 08:56:05 +0000 MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neurotoxicity. Exposure to chronic stress has been shown to augment MDMA-induced 5-HT neurotoxicity. Here, we examine the transcriptional responses in the hippocampus to MDMA treatment of control rats and rats exposed to chronic stress. MDMA altered the expression of genes that regulate unfolded protein binding, protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling. In stressed rats, the gene expression profile in response to MDMA was altered to affect sensory processing and responses to tissue damage in nerve sheaths. Subsequent treatment with MDMA also markedly altered the genetic responses to stress such that the stress-induced downregulation of genes related to the circadian rhythm was reversed. The data support the view that MDMA-induced transcriptional responses accompany the persistent effects of this drug on neuronal structure/function. In addition, MDMA treatment alters the stress-induced transcriptional signature. Georg F. Weber, Bethann N. Johnson, Bryan K. Yamamoto, and Gary A. Gudelsky Copyright © 2014 Georg F. Weber et al. All rights reserved. GRIN2B Gene and Associated Brain Cortical White Matter Changes in Bipolar Disorder: A Preliminary Combined Platform Investigation Mon, 30 Dec 2013 18:55:20 +0000 Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (), right frontal region (), left parietal region (), left occipital region (), right occipital region (), and left cingulate gyrus (). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD. Carissa Nadia Kuswanto, Min Yi Sum, Christopher Ren Zhi Thng, Yi Bin Zhang, Guo Liang Yang, Wieslaw Lucjan Nowinski, Yih Yian Sitoh, Chian Ming Low, and Kang Sim Copyright © 2013 Carissa Nadia Kuswanto et al. All rights reserved. Comparison of Neurologic and Radiographic Outcomes with Solitaire versus Merci/Penumbra Systems for Acute Stroke Intervention Mon, 30 Dec 2013 12:01:02 +0000 Background and Purpose. The Solitaire Flow Restoration was approved by the FDA in 2012 for mechanical thrombolysis of proximal occlusion of intracranial arteries. To compare the Solitaire FR device and the Merci/Penumbra (previously FDA approved) systems in terms of safety, clinical outcomes, and efficacy including radiographic brain parenchymal salvage. Methods. Thirty-one consecutive patients treated with the Solitaire and 20 patients with comparable baseline characteristics treated with Merci or Penumbra systems were included in the study. Primary outcome measures included recanalization rate and modified Rankin Scale score at followup. Secondary outcomes included length of procedure, incidence of symptomatic intracranial hemorrhage, 90-day mortality, and radiographic analysis of percentage area salvage. Results. Compared with the Merci/Penumbra group, the Solitaire group showed a statistically significant improvement in favorable outcomes (mRS ≤ 2) (69% versus 35%, ) and symptomatic ICH rate (0 versus 15%, ) with a trend towards higher recanalization rates (93.5% versus 75%, ) and shorter length of procedure (58.5 min versus 70.8 min, ). Radiographic comparison also showed a significantly larger area of salvage in the Solitaire group (81.9% versus 71.9%, ). Conclusion. Our study suggests that the Solitaire system allows faster, safer, and more efficient thrombectomy than Merci or Penumbra systems. Shannon Hann, Nohra Chalouhi, Robert Starke, Ashish Gandhe, Michael Koltz, Thana Theofanis, Pascal Jabbour, L. Fernando Gonzalez, Robert Rosenwasser, and Stavropoula Tjoumakaris Copyright © 2013 Shannon Hann et al. All rights reserved. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury Sun, 29 Dec 2013 16:24:37 +0000 Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. Daniele Tomassoni, Francesco Amenta, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Innocent E. Nwankwo, Alessandra Pacini, and Seyed Khosrow Tayebati Copyright © 2013 Daniele Tomassoni et al. All rights reserved. Atrophy and Primary Somatosensory Cortical Reorganization after Unilateral Thoracic Spinal Cord Injury: A Longitudinal Functional Magnetic Resonance Imaging Study Sun, 29 Dec 2013 14:38:31 +0000 The effects of traumatic spinal cord injury (SCI) on the changes in the central nervous system (CNS) over time may depend on the dynamic interaction between the structural integrity of the spinal cord and the capacity of the brain plasticity. Functional magnetic resonance imaging (fMRI) was used in a longitudinal study on five rhesus monkeys to observe cerebral activation during upper limb somatosensory tasks in healthy animals and after unilateral thoracic SCI. The changes in the spinal cord diameters were measured, and the correlations among time after the lesion, structural changes in the spinal cord, and primary somatosensory cortex (S1) reorganization were also determined. After SCI, activation of the upper limb in S1 shifted to the region which generally dominates the lower limb, and the rostral spinal cord transverse diameter adjacent to the lesion exhibited obvious atrophy, which reflects the SCI-induced changes in the CNS. A significant correlation was found among the time after the lesion, the spinal cord atrophy, and the degree of contralateral S1 reorganization. The results indicate the structural changes in the spinal cord and the dynamic reorganization of the cerebral activation following early SCI stage, which may help to further understand the neural plasticity in the CNS. Jia-Sheng Rao, Ma Manxiu, Can Zhao, Yue Xi, Zhao-Yang Yang, Liu Zuxiang, and Xiao-Guang Li Copyright © 2013 Jia-Sheng Rao et al. All rights reserved. Hippocampal Gene Expression of Deiodinases 2 and 3 and Effects of 3,5-Diiodo-L-Thyronine T2 in Mouse Depression Paradigms Tue, 10 Dec 2013 08:57:50 +0000 Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3′,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated. Natalyia Markova, Anton Chernopiatko, Careen A. Schroeter, Dmitry Malin, Aslan Kubatiev, Sergey Bachurin, João Costa-Nunes, Harry M. W. Steinbusch, and Tatyana Strekalova Copyright © 2013 Natalyia Markova et al. All rights reserved. Endovascular Treatment of Cerebral Mycotic Aneurysm: A Review of the Literature and Single Center Experience Mon, 09 Dec 2013 09:48:41 +0000 The management of mycotic aneurysm has always been subject to controversy. The aim of this paper is to review the literature on the intracranial infected aneurysm from pathogenesis till management while focusing mainly on the endovascular interventions. This novel solution seems to provide additional benefits and long-term favorable outcomes. Mario Zanaty, Nohra Chalouhi, Robert M. Starke, Stavropoula Tjoumakaris, L. Fernando Gonzalez, David Hasan, Robert Rosenwasser, and Pascal Jabbour Copyright © 2013 Mario Zanaty et al. All rights reserved. Enhanced Intensity Dependence as a Marker of Low Serotonergic Neurotransmission in High Optimistic College Students Sun, 08 Dec 2013 14:36:25 +0000 Positive psychology focuses were on the merits of individuals, such as optimism and positive attitude, and the subsequent cultivation of these virtues. Optimism or pessimism is a significant predictor of physical health outcomes. The present study examined whether optimism or pessimism is associated with the loudness dependence of auditory evoked potentials (LDAEP), a biological indicator of serotonergic neurotransmission, for the N1, P2, and N1/P2 peaks in college students. The amplitudes and amplitude-stimulus intensity function (ASF) slopes of the N1, P2, and N1/P2 peaks were determined in the 24 (10 males) high optimistic and 24 (14 males) high pessimistic individuals. Significantly higher P2 ASF slopes were found in the optimistic group relative to the pessimistic group. Concerning peaks and ASF slopes of N1 and N1/P2, no significant differences were observed. Our results suggest that the serotonergic neurotransmission of the high optimistic college students was inferior to that of the pessimistic ones. Further investigations are needed to provide sufficient support for our results. Jibiao Zhang, Daxing Wu, Shuqiao Yao, Yunxuan Xu, and Xuejing Lu Copyright © 2013 Jibiao Zhang et al. All rights reserved. Cerebral Blood Flow Dynamics and Head-of-Bed Changes in the Setting of Subarachnoid Hemorrhage Mon, 25 Nov 2013 13:48:22 +0000 Head-of-bed (HOB) elevation is usually restricted in patients with aneurysmal subarachnoid hemorrhage (SAH). The goal of this study is to correlate HOB changes ( and ) with cerebral blood flow using transcranial Doppler (TCD) and thermal diffusion probe in SAH patients. Thirteen patients with SAH were prospectively enrolled in the study. Eight patients underwent placement of a thermal diffusion probe for regional CBF measurement. CBF values were measured with the patients in flat () and upright sitting positions () at days 3, 7, and 10. The average increase in blood flow velocity when changing HOB from to was 7.8% on day 3, 0.1% on day 7, and 13.1% on day 10. The middle cerebral artery had the least changes in velocity. The average regional CBF measurement was 22.7 ± 0.3 mL/100 g/min in the supine position and 23.6 ± 9.1 mg/100 g/min in the sitting position. The changes were not statistically significant. None of the patients developed clinical cerebral vasospasm. Changing HOB position in the setting of SAH did not significantly affect cerebral or regional blood flow. These data suggest that early mobilization should be considered given the detrimental effects of prolonged bed rest. David K. Kung, Nohra Chalouhi, Pascal M. Jabbour, Robert M. Starke, Aaron S. Dumont, H. Richard Winn, Matthew A. Howard III, and David M. Hasan Copyright © 2013 David K. Kung et al. All rights reserved. Role of Stenting for Intracranial Atherosclerosis in the Post-SAMMPRIS Era Wed, 20 Nov 2013 15:47:25 +0000 Introduction. The initial promise of endovascular stenting for the treatment of intracranial atherosclerotic disease (ICAD) has been tempered by the results of the SAMMPRIS trial which demonstrated better outcomes with medical management compared to stenting for symptomatic ICAD. We review post-SAMMPRIS ICAD stenting outcomes. Methods. A comprehensive literature search was performed using PubMed to identify all ICAD stenting series published after the SAMMPRIS in September 2011. The type and design of the stent, number of patients and lesions, inclusion criteria, and clinical and angiographic outcomes were noted. Results. From October 2011 to August 2013, 19 ICAD stenting series were identified describing the interventional outcomes for 2,196 patients with 2,314 lesions. Of the 38 different stents used, 87% were balloon-expandable stents (BESs) and 13% were self-expanding stents. The median minimum stenosis was 50%. The median rates of technical success rate, postprocedural ischemic events, and symptomatic in-stent restenosis (ISR) were 98% (range 87–100%), 9.4% (range 0–25%), and 2.7% (range 0–11.1%), respectively. The median follow-up durations were one to 67 months. Conclusions. The management of severe ICAD remains controversial. Future trials are needed to define the optimal patient, lesion, and stent characteristics which will portend the best outcomes with intervention. Dale Ding, Robert M. Starke, R. Webster Crowley, and Kenneth C. Liu Copyright © 2013 Dale Ding et al. All rights reserved. Chronic Traumatic Encephalopathy and Suicide: A Systematic Review Sun, 17 Nov 2013 10:15:41 +0000 Traumatic brain injury (TBI) is a global health concern, and the recent literature reports that a single mild TBI can result in chronic traumatic encephalopathy (CTE). It has been suggested that CTE may lead to death by suicide, raising important prevention, treatment, and policy implications. Thus, we conducted a systematic review of the medical literature to answer the key question: What is the existing evidence in support of a relationship between CTE and suicide? Systematic searches of CTE and suicide yielded 85 unique abstracts. Seven articles were identified for full text review. Only two case series met inclusion criteria and included autopsies from 17 unique cases, 5 of whom died by suicide. Neither studies used blinding, control cases, or systematic data collection regarding TBI exposure and/or medical/neuropsychiatric history. The identified CTE literature revealed divergent opinions regarding neuropathological elements of CTE and heterogeneity regarding clinical manifestations. Overall quality of evidence regarding a relationship between CTE and suicide was rated as very low using Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) criteria. Further studies of higher quality and methodological rigor are needed to determine the existence and nature of any relationship between CTE and suicide. Hal S. Wortzel, Robert D. Shura, and Lisa A. Brenner Copyright © 2013 Hal S. Wortzel et al. All rights reserved. Estrogen Signaling through Estrogen Receptor Beta and G-Protein-Coupled Estrogen Receptor 1 in Human Cerebral Vascular Endothelial Cells: Implications for Cerebral Aneurysms Tue, 12 Nov 2013 09:12:11 +0000 Little is known about estrogen receptors and their signaling mechanisms in human cerebral vascular endothelial cells, which is important for understanding cerebral aneurysm pathogenesis in menopausal and postmenopausal women. Estrogen receptor beta (ERβ) and G-protein-coupled receptor 1 (GPER1) were immunocytochemically identified in human cerebral vascular endothelial cells (HCVECs). ERβ was mainly located at the nuclei of the cells while GPER1 was located at the plasma membrane. Interaction events between 17β-estradiol and ERβ or GPER1 in HCVECs were evaluated by in situ proximity ligation assay. The number of interaction events between 17β-estradiol and ERβ was positively correlated with 17β-estradiol concentrations (, ). The interaction events between 17β-estradiol and GPER1 were dose responsive. Our data support HCVECs to serve as a suitable cellular model for studying cerebral aneurysm pathogenesis in menopausal and postmenopausal women. Subtypes of estrogen receptors and their signaling mechanisms identified in HCVECs could be applicable for developing estrogen-like compounds to specifically bind to a subtype of estrogen receptors with greater specific action on the cerebral arteries, without the estrogen-dependent side effects on the reproductive organs, to prevent cerebral aneurysm formation in menopausal and postmenopausal woman. Jian Tu and Nurul F. Jufri Copyright © 2013 Jian Tu and Nurul F. Jufri. All rights reserved. Topography of Striate-Extrastriate Connections in Neonatally Enucleated Rats Thu, 03 Oct 2013 18:13:37 +0000 It is known that retinal input is necessary for the normal development of striate cortex and its corticocortical connections, but there is little information on the role that retinal input plays in the development of retinotopically organized connections between V1 and surrounding visual areas. In nearly all lateral extrastriate areas, the anatomical and physiological representation of the nasotemporal axis of the visual field mirrors the representation of this axis in V1. To determine whether the mediolateral topography of striate-extrastriate projections is preserved in neonatally enucleated rats, we analyzed the patterns of projections resulting from tracer injections placed at different sites along the mediolateral axis of V1. We found that the correlation between the distance from injection sites to the lateral border of V1 and the distance of the labeling patterns in area 18a was strong in controls and much weaker in enucleates. Data from pairs of injections in the same animal revealed that the separation of area 18a projection fields for a given separation of injection sites was more variable in enucleated than in control rats. Our analysis of single and double tracer injections suggests that neonatal bilateral enucleation weakens, but not completely abolishes, the mediolateral topography in area 18a. Robyn J. Laing, Jurate Lasiene, and Jaime F. Olavarria Copyright © 2013 Robyn J. Laing et al. All rights reserved. Reliabilities of Mental Rotation Tasks: Limits to the Assessment of Individual Differences Mon, 30 Sep 2013 14:28:26 +0000 Mental rotation tasks with objects and body parts as targets are widely used in cognitive neuropsychology. Even though these tasks are well established to study between-groups differences, the reliability on an individual level is largely unknown. We present a systematic study on the internal consistency and test-retest reliability of individual differences in mental rotation tasks comparing different target types and orders of presentations. In total participants ( for the retest) completed the mental rotation tasks with hands, feet, faces, and cars as targets. Different target types were presented in either randomly mixed blocks or blocks of homogeneous targets. Across all target types, the consistency (split-half reliability) and stability (test-retest reliabilities) were good or acceptable both for intercepts and slopes. At the level of individual targets, only intercepts showed acceptable reliabilities. Blocked presentations resulted in significantly faster and numerically more consistent and stable responses. Mental rotation tasks—especially in blocked variants—can be used to reliably assess individual differences in global processing speed. However, the assessment of the theoretically important slope parameter for individual targets requires further adaptations to mental rotation tests. Gerrit Hirschfeld, Meinald T. Thielsch, and Boris Zernikow Copyright © 2013 Gerrit Hirschfeld et al. All rights reserved. Altered Functional Connectivity within and between Brain Modules in Absence Epilepsy: A Resting-State Functional Magnetic Resonance Imaging Study Thu, 26 Sep 2013 10:17:51 +0000 Functional connectivity has been correlated with a patient’s level of consciousness and has been found to be altered in several neuropsychiatric disorders. Absence epilepsy patients, who experience a loss of consciousness, are assumed to suffer from alterations in thalamocortical networks; however, previous studies have not explored the changes at a functional module level. We used resting-state functional magnetic resonance imaging to examine the alteration in functional connectivity that occurs in absence epilepsy patients. By parcellating the brain into 90 brain regions/nodes, we uncovered an altered functional connectivity within and between functional modules. Some brain regions had a greater number of altered connections and therefore behaved as key nodes in the changed network pattern; these regions included the superior frontal gyrus, the amygdala, and the putamen. In particular, the superior frontal gyrus demonstrated both an increased value of connections with other nodes of the frontal default mode network and a decreased value of connections with the limbic system. This divergence is positively correlated with epilepsy duration. These findings provide a new perspective and shed light on how functional connectivity and the balance of within/between module connections may contribute to both the state of consciousness and the development of absence epilepsy. Cui-Ping Xu, Shou-Wen Zhang, Tie Fang, Ma Manxiu, Qian Chencan, Chen Huafu, Hong-Wei Zhu, Yong-Jie Li, and Liu Zuxiang Copyright © 2013 Cui-Ping Xu et al. All rights reserved. Participation of Chloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture Thu, 19 Sep 2013 08:16:45 +0000 Human amniotic fluid and a mixture of eight fatty acids (FAT-M) identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg%) produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement of γ-aminobutyric acid-A () receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, three receptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg), benzodiazepine antagonist flumazenil (5 mg/kg), and noncompetitive chloride channel antagonist picrotoxin (1 mg/kg). The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. The antagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects through receptor chloride channels. Juan Francisco Rodríguez-Landa, Rosa Isela García-Ríos, Jonathan Cueto-Escobedo, Blandina Bernal-Morales, and Carlos M. Contreras Copyright © 2013 Juan Francisco Rodríguez-Landa et al. All rights reserved. Direct Evaluation of L-DOPA Actions on Neuronal Activity of Parkinsonian Tissue In Vitro Tue, 17 Sep 2013 13:45:28 +0000 Physiological and biochemical experiments in vivo and in vitro have explored striatal receptor signaling and neuronal excitability to posit pathophysiological models of Parkinson's disease. However, when therapeutic approaches, such as dopamine agonists, need to be evaluated, behavioral tests using animal models of Parkinson's disease are employed. To our knowledge, recordings of population neuronal activity in vitro to assess anti-Parkinsonian drugs and the correlation of circuit dynamics with disease state have only recently been attempted. We have shown that Parkinsonian pathological activity of neuronal striatal circuits can be characterized in in vitro cerebral tissue. Here, we show that calcium imaging techniques, capable of recording dozens of neurons simultaneously with single-cell resolution, can be extended to assess the action of therapeutic drugs. We used L-DOPA as a prototypical anti-Parkinsonian drug to show the efficiency of this proposed bioassay. In a rodent model of early Parkinson's disease, Parkinsonian neuronal activity can be returned to control levels by the bath addition of L-DOPA in a reversible way. This result raises the possibility to use calcium imaging techniques to measure, quantitatively, the actions of anti-Parkinsonian drugs over time and to obtain correlations with disease evolution and behavior. Víctor Plata, Mariana Duhne, Jesús E. Pérez-Ortega, Janet Barroso-Flores, Elvira Galarraga, and José Bargas Copyright © 2013 Víctor Plata et al. All rights reserved. Locally Applied Valproate Enhances Survival in Rats after Neocortical Treatment with Tetanus Toxin and Cobalt Chloride Sat, 14 Sep 2013 15:28:21 +0000 Purpose. In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl2). Methods. In rats, VPA () or sodium chloride (NaCl) () containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl2. Video-EEG monitoring was performed with intracortical depth electrodes. Results. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (). In both groups, witnessed deaths occurred in the context of seizures. At least of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures. Conclusions. The novel TeT/CoCl2 approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms. Dirk-Matthias Altenmüller, Jonas M. Hebel, Michael P. Rassner, Silvanie Volz, Thomas M. Freiman, Thomas J. Feuerstein, and Josef Zentner Copyright © 2013 Dirk-Matthias Altenmüller et al. All rights reserved. The StartReact Effect on Self-Initiated Movements Wed, 11 Sep 2013 09:54:47 +0000 Preparation of the motor system for movement execution involves an increase in excitability of motor pathways. In a reaction time task paradigm, a startling auditory stimulus (SAS) delivered together with the imperative signal (IS) shortens reaction time significantly. In self-generated tasks we considered that an appropriately timed SAS would have similar effects. Eight subjects performed a ballistic wrist extension in two blocks: reaction, in which they responded to a visual IS, and action, in which they moved when they wished within a predetermined time window. In 20–25% of the trials, a SAS was applied. We recorded electromyographic activity of wrist extension and wrist movement kinematic variables. No effects of SAS were observed in action trials when movement was performed before or long after SAS application. However, a cluster of action trials was observed within 200 ms after SAS. These trials showed larger EMG bursts, shorter movement time, shorter time to peak velocity, and higher peak velocity than other action trials ( for all), with no difference from Reaction trials containing SAS. The results show that SAS influences the execution of self-generated human actions as it does with preprogrammed reaction time tasks during the assumed building up of preparatory activity before execution of the willed motor action. J. M. Castellote, M. E. L. Van den Berg, and J. Valls-Solé Copyright © 2013 J. M. Castellote et al. All rights reserved. Angiotensin II AT1 Receptors Are Involved in Neuronal Activation Induced by Amphetamine in a Two-Injection Protocol Sun, 08 Sep 2013 08:09:21 +0000 It was already found that Ang II AT1 receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine, and such changes are related to the development of behavioral and neurochemical sensitization. The induction of the immediately early gene c-fos has been used to define brain activated areas by amphetamine. Our aim was to evaluate the participation of AT1 receptors in the neuronal activation induced by amphetamine sensitization. The study examined the c-fos expression in mesocorticolimbic areas induced by amphetamine challenge (0.5 mg/kg i.p) in animals pretreated with candesartan, a selective AT1 receptor blocker (3 mg/kg p.o × 5 days), and amphetamine (5 mg/kg i.p) 3 weeks before the challenge. Increased c-fos immunoreactivity was found in response to the amphetamine challenge in the dorsomedial caudate-putamen and nucleus accumbens, and both responses were blunted by the AT1 receptor blocker pretreatment. In the infralimbic prefrontal cortex, increased c-fos immunoreactivity was found in response to amphetamine and saline challenge, and both were prevented by the AT1 receptor blocker. No differences were found neither in ventral tegmental area nor prelimbic cortex between groups. Our results indicate an important role for brain Ang II in the behavioral and neuronal sensitization induced by amphetamine. Maria Constanza Paz, Natalia Andrea Marchese, Liliana M. Cancela, and Claudia Bregonzio Copyright © 2013 Maria Constanza Paz et al. All rights reserved. Neuroprotective Effect of Ginseng against Alteration of Calcium Binding Proteins Immunoreactivity in the Mice Hippocampus after Radiofrequency Exposure Thu, 29 Aug 2013 11:39:19 +0000 Calcium binding proteins (CaBPs) such as calbindin D28-k, parvalbumin, and calretinin are able to bind Ca2+ with high affinity. Changes in Ca2+ concentrations via CaBPs can disturb Ca2+ homeostasis. Brain damage can be induced by the prolonged electromagnetic field (EMF) exposure with loss of interacellular Ca2+ balance. The present study investigated the radioprotective effect of ginseng in regard to CaBPs immunoreactivity (IR) in the hippocampus through immunohistochemistry after one-month exposure at 1.6 SAR value by comparing sham control with exposed and ginseng-treated exposed groups separately. Loss of dendritic arborization was noted with the CaBPs in the Cornu Ammonis areas as well as a decrease of staining intensity of the granule cells in the dentate gyrus after exposure while no loss was observed in the ginseng-treated group. A significant difference in the relative mean density was noted between control and exposed groups but was nonsignificant in the ginseng-treated group. Decrease in CaBP IR with changes in the neuronal staining as observed in the exposed group would affect the hippocampal trisynaptic circuit by alteration of the Ca2+ concentration which could be prevented by ginseng. Hence, ginseng could contribute as a radioprotective agent against EMF exposure, contributing to the maintenance of Ca2+ homeostasis by preventing impairment of intracellular Ca2+ levels in the hippocampus. Dhiraj Maskey, Jin-Koo Lee, Hak Rim Kim, and Hyung-Gun Kim Copyright © 2013 Dhiraj Maskey et al. All rights reserved. Microtubule-Associated Proteins in Mesial Temporal Lobe Epilepsy with and without Psychiatric Comorbidities and Their Relation with Granular Cell Layer Dispersion Tue, 27 Aug 2013 11:45:35 +0000 Background. Despite strong association between epilepsy and psychiatric comorbidities, biological substrates are unknown. We have previously reported decreased mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and increased in those with major depression. Microtubule associated proteins (MAPs) are essentially involved in dendritic and synaptic sprouting. Methods. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, and MTLE + interictal psychosis derived from epilepsy surgery and control necropsies were investigated for neuronal density, granular layer dispersion, and MAP2 and tau immunohistochemistry. Results. Altered MAP2 and tau expression in MTLE and decreased tau expression in MTLE with psychosis were found. Granular layer dispersion correlated inversely with verbal memory scores, and with MAP2 and tau expression in the entorhinal cortex. Patients taking fluoxetine showed increased neuronal density in the granular layer and those taking haloperidol decreased neuronal density in CA3 and subiculum. Conclusions. Our results indicate relations between MAPs, granular layer dispersion, and memory that have not been previously investigated. Differential MAPs expression in human MTLE hippocampi with and without psychiatric comorbidities suggests that psychopathological states in MTLE rely on differential morphological and possibly neurochemical backgrounds. This clinical study was approved by our institution’s Research Ethics Board (HC-FMRP no. 1270/2008) and is registered under the Brazilian National System of Information on Ethics in Human Research (SISNEP) no. 0423.0.004.000-07. Ludmyla Kandratavicius, Mariana Raquel Monteiro, Jaime Eduardo Hallak, Carlos Gilberto Carlotti Jr., Joao Alberto Assirati Jr., and Joao Pereira Leite Copyright © 2013 Ludmyla Kandratavicius et al. All rights reserved. Effects of an Alpha7 Nicotinic Receptor Agonist and Stress on Spatial Memory in an Animal Model of Alzheimer's Disease Sat, 24 Aug 2013 09:21:05 +0000 The aim of the present study was to test the effects of PNU-282987 on spatial learning and memory and hippocampal neurogenesis in both intact and chronically stressed transgenic mice. Transgenic mice with susceptibility to Alzheimer's disease (AD) under immobilization stress and not-stressed animals receiving 0 and 1 mg/kg of PNU-282987 (PNU) were evaluated in a water maze task. The effects of PNU and stress on proliferation of new cells in the hippocampus of these animals were also assessed. The latency to escape the platform was significantly higher in transgenic stressed mice compared to those in the wild stressed group, as well as in transgenic animals without PNU compared to control wild group. On retention of the task, differences emerged on stressed wild animals, PNU wild group, and stressed wild mice receiving PNU. However, no significant differences were detected on new cell proliferation. The results of the present study did not show any impact of stress in acquisition of a spatial task both in wild and transgenic mice. No clear effects of PNU on acquisition of a spatial task in transgenic mice with susceptibility to AD were detected. Although PNU and stress effects were detected on retention of the task in wild animals, no changes were noted in transgenic mice. Paloma Vicens, Diana Ribes, Luis Heredia, Margarita Torrente, and José L. Domingo Copyright © 2013 Paloma Vicens et al. All rights reserved. Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells Sun, 18 Aug 2013 10:51:56 +0000 Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology. Anahita Rahmani, Danial Kheradmand, Peyman Keyhanvar, Alireza Shoae-Hassani, and Amir Darbandi-Azar Copyright © 2013 Anahita Rahmani et al. All rights reserved. The Role of Neuropeptides in Suicidal Behavior: A Systematic Review Tue, 06 Aug 2013 13:32:15 +0000 There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF), VGF, cholecystokinin, substance P, and neuropeptide Y (NPY), which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper. Gianluca Serafini, Maurizio Pompili, Daniel Lindqvist, Yogesh Dwivedi, and Paolo Girardi Copyright © 2013 Gianluca Serafini et al. All rights reserved. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation Thu, 01 Aug 2013 10:56:06 +0000 NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms. Qian-Kun Yang, Jia-Xiang Xiong, and Zhong-Xiang Yao Copyright © 2013 Qian-Kun Yang et al. All rights reserved. Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice Thu, 01 Aug 2013 10:17:14 +0000 Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients. Abhinoy Kishore, Anurag Kanaujia, Soma Nag, A. M. Rostami, Lawrence C. Kenyon, Kenneth S. Shindler, and Jayasri Das Sarma Copyright © 2013 Abhinoy Kishore et al. All rights reserved. The Effect of Ranitidine on Olanzapine-Induced Weight Gain Tue, 30 Jul 2013 10:57:56 +0000 Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI) was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6) kg at baseline. Thirty-three subjects (63.5%) had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend’s slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with 201009112181N5. Fatemeh Ranjbar, Alireza Ghanepour, Homayoun Sadeghi-Bazargani, Mahbob Asadlo, and Amineh Alizadeh Copyright © 2013 Fatemeh Ranjbar et al. All rights reserved. Serum Ghrelin Is Associated with Verbal Learning and Adiposity in a Sample of Healthy, Fit Older Adults Thu, 18 Jul 2013 08:46:07 +0000 The purpose of the present investigation was to determine the relationship between serum ghrelin concentrations, adiposity, and verbal learning in a group of healthy, fit older adults. Participants were 28 healthy older adults (age: yrs, BMI: ). Participants reported to the laboratory and basic anthropometric data were collected, followed by a blood draw to quantify serum ghrelin. Participants then underwent cognitive testing that included the revised Hopkins Verbal Learning Test (HVLT), as well as the Mini-Mental Status Exam (MMSE). The results of the MMSE test revealed that the volunteers were cognitively intact (MMSE ). A significant correlation emerged between serum ghrelin concentrations, 2 trials of the HVLT (Trial 1: , ; Trial 2: , ), and the sum of three-site skinfold analysis (). Based upon the aforementioned relationships, it appears that fasting levels of serum ghrelin are related to both verbal learning and adiposity in healthy, fit older adults. David Bellar, Ellen L. Glickman, Lawrence W. Judge, and John Gunstad Copyright © 2013 David Bellar et al. All rights reserved. Modulation of Neurological Deficits and Expression of Glutamate Receptors during Experimental Autoimmune Encephalomyelitis after Treatment with Selected Antagonists of Glutamate Receptors Mon, 08 Jul 2013 11:24:24 +0000 The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p.i.), but starting from 8 d.p.i. to 25 d.p.i., we observed a significant elevation of mGluR1 and mGluR5 protein expression by about 20% and NMDA protein expression by about 10% over the control at 25 d.p.i. The changes in protein levels were accompanied by changes in mRNA expression of group I mGluRs and NMDARs. During the late disease phase (20–25 d.p.i.), the mRNA expression levels reached 300% of control values. In contrast, treatment with individual receptor antagonists resulted in a reduction of mRNA levels relative to untreated animals. Grzegorz Sulkowski, Beata Dąbrowska-Bouta, and Lidia Strużyńska Copyright © 2013 Grzegorz Sulkowski et al. All rights reserved. Efficacy of Iranian Traditional Medicine in the Treatment of Epilepsy Sun, 07 Jul 2013 14:17:08 +0000 Epilepsy is a brain disorder which affects about 50 million people worldwide. Ineffectiveness of the drugs in some cases and the serious side effects and chronic toxicity of the antiepileptic drugs lead to use of herbal medicine as a form of complementary and alternative medicine. In this review modern evidences for the efficacy of antiepileptic medicinal plants in Traditional Iranian Medicine (TIM) will be discussed. For this purpose electronic databases including PubMed, Scopus, Sciencedirect, and Google Scholar were searched for each of the antiepileptic plants during 1970-February 2013.Anticonvulsant effect of some of the medicinal plants mentioned in TIM like Anacyclus pyrethrum, Pimpinella anisum, Nigella sativa, and Ferula gummosa was studied with different models of seizure. Also for some of these plants like Nigella sativa or Piper longum the active constituent responsible for antiepileptic effect was isolated and studied. For some of the herbal medicine used in TIM such as Pistacia lentiscus gum (Mastaki), Bryonia alba (Fashra), Ferula persica (Sakbinaj), Ecballium elaterium (Ghesa-al Hemar), and Alpinia officinarum (Kholanjan) there is no or not enough studies to confirm their effectiveness in epilepsy. It is suggested that an evaluation of the effects of these plants on different epileptic models should be performed. Mehri Abdollahi Fard and Asie Shojaii Copyright © 2013 Mehri Abdollahi Fard and Asie Shojaii. All rights reserved. Use of Fidji Cervical Cage in the Treatment of Cervical Spinal Cord Injury without Radiographic Abnormality Mon, 17 Jun 2013 18:47:51 +0000 Spinal cord injury without radiographic abnormality (SCIWORA) is a rare condition seen in adults. Many interbody fusion cages have been developed for its treatment, but clinical studies of Fidji cervical cage are still scarce. A total number of five patients (four male and one female) were reviewed. The ages of the patients ranged from 40 to 60 years. All the patients underwent neurological and radiological examinations. Neurological and functional outcomes were assessed on the basis of Frankel’s grade. Three of the patients were Frankel B, and the rest two were Frankel C. Magnetic resonance imaging was also performed for the evaluation of spinal cord and intervertebral disc injury. Anterior cervical discectomy and Fidji cervical cage fusion were performed for all. The fusion status was evaluated on the basis of X-rays. After surgical intervention, the clinical symptoms improved for all the patients. The disc interspaces in all the patients achieved solid union at final follow-up. Fidji cervical cage is very efficient in achieving cervical fusion in patients with SCIWORA. There are few complications associated with the use of this cage, and the functional and neurological outcomes are satisfactory. Sheng-Li Huang, Hong-Wei Yan, and Kun-Zheng Wang Copyright © 2013 Sheng-Li Huang et al. All rights reserved. Reproducibility in Nerve Morphometry: Comparison between Methods and among Observers Thu, 13 Jun 2013 18:00:25 +0000 We investigated the reproducibility of a semiautomated method (computerized with manual intervention) for nerve morphometry (counting and measuring myelinated fibers) between three observers with different levels of expertise and experience with the method. Comparisons between automatic (fully computerized) and semiautomated morphometric methods performed by the same computer software using the same nerve images were also performed. Sural nerves of normal adult rats were used. Automatic and semiautomated morphometry of the myelinated fibers were made through the computer software KS-400. Semiautomated morphometry was conducted by three independent observers on the same images, using the semiautomated method. Automatic morphometry overestimated the myelin sheath area, thus overestimating the myelinated fiber size and underestimating the axon size. Fiber distributions overestimation was of 0.5 μm. For the semiautomated morphometry, no differences were found between observers for myelinated fiber and axon size distributions. Overestimation of the myelin sheath size of normal fibers by the fully automatic method might have an impact when morphometry is used for diagnostic purposes. We suggest that not only semiautomated morphometry results can be compared between different centers in clinical trials but it can also be performed by more than one investigator in one single experiment, being a reliable and reproducible method. Antônio Paulo da Costa Bilego Neto, Fernando Braga Cassiano Silveira, Greice Anne Rodrigues da Silva, Luciana Sayuri Sanada, and Valéria Paula Sassoli Fazan Copyright © 2013 Antônio Paulo da Costa Bilego Neto et al. All rights reserved. Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress Thu, 13 Jun 2013 13:51:42 +0000 This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, ( per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for 15 days. Novel object recognition, open field, and forced swim tests were conducted after the stress procedure. Serum estradiol, ACTH and corticosterone levels were measured using commercially available ELISA kits. Lower serum estradiol level and uterine weight with higher weight gain were observed in OVX rats compared to sham-operated controls. Serum ACTH, and corticosterone levels were higher in stressed compared to non-stressed groups. Memory deficit and anxiety- and depressive-like behaviour were significantly increased in stressed compared to non-stressed OVX rats but these changes were not seen in sham-operated controls. These results suggest that the high circulating corticosterone acts synergistically with low circulating estradiol to exert negative effects on mood and memory function. Badriya Al-Rahbi, Rahimah Zakaria, Zahiruddin Othman, Asma’ Hassan, Sangu Muthuraju, and Wan Mohd Zahiruddin Wan Mohammad Copyright © 2013 Badriya Al-Rahbi et al. All rights reserved. Is There a Causal Link between Inflammation and Dementia? Thu, 06 Jun 2013 08:39:45 +0000 Neuroinflammation is a constant event in Alzheimer’s disease (AD), but the current knowledge is insufficient to state whether inflammation is a cause, a promoter, or simply a secondary phenomenon in this inexorably progressive ailment. In the current paper, we review research data showing that inflammation is not a prerequisite for onset of dementia, and, although it may worsen the course of the disease, recent evidence shows that chronic inhibition of inflammatory pathways is not necessarily beneficial for patients. Prospective clinical trials with anti-inflammatory drugs failed to stop disease progression, measurements of inflammatory markers in serum and cerebrospinal fluid of patients yielded contradictory results, and recent bench research proved undoubtedly that neuroinflammation has a protective side as well. Knockout animal models for TNFRs or ILRs do not seem to prevent the pathology or the cognitive decline, but quite the contrary. In AD, the therapeutic intervention on inflammatory pathways still has a research future, but its targets probably need reevaluation. Ana-Maria Enciu and Bogdan O. Popescu Copyright © 2013 Ana-Maria Enciu and Bogdan O. Popescu. All rights reserved. The Golden Ratio of Gait Harmony: Repetitive Proportions of Repetitive Gait Phases Tue, 04 Jun 2013 11:34:19 +0000 In nature, many physical and biological systems have structures showing harmonic properties. Some of them were found related to the irrational number known as the golden ratio that has important symmetric and harmonic properties. In this study, the spatiotemporal gait parameters of 25 healthy subjects were analyzed using a stereophotogrammetric system with 25 retroreflective markers located on their skin. The proportions of gait phases were compared with , the value of which is about 1.6180. The ratio between the entire gait cycle and stance phase resulted in 1.620 ± 0.058, that between stance and the swing phase was 1.629 ± 0.173, and that between swing and the double support phase was 1.684 ± 0.357. All these ratios did not differ significantly from each other (, , repeated measure analysis of variance) or from (, resp., t-tests). The repetitive gait phases of physiological walking were found in turn in repetitive proportions with each other, revealing an intrinsic harmonic structure. Harmony could be the key for facilitating the control of repetitive walking. Harmony is a powerful unifying factor between seemingly disparate fields of nature, including human gait. Marco Iosa, Augusto Fusco, Fabio Marchetti, Giovanni Morone, Carlo Caltagirone, Stefano Paolucci, and Antonella Peppe Copyright © 2013 Marco Iosa et al. All rights reserved. An Entropy-Based Model for Basal Ganglia Dysfunctions in Movement Disorders Thu, 16 May 2013 19:12:11 +0000 During this last decade, nonlinear analyses have been used to characterize the irregularity that exists in the neuronal data stream of the basal ganglia. In comparison to linear parameters for disparity (i.e., rate, standard deviation, and oscillatory activities), nonlinear analyses focus on complex patterns that are composed of groups of interspike intervals with matching lengths but not necessarily contiguous in the data stream. In light of recent animal and clinical studies, we present a review and commentary on the basal ganglia neuronal entropy in the context of movement disorders. Olivier Darbin, Daniel Dees, Anthony Martino, Elizabeth Adams, and Dean Naritoku Copyright © 2013 Olivier Darbin et al. All rights reserved. Effect of Brain-to-Skull Conductivity Ratio on EEG Source Localization Accuracy Wed, 17 Apr 2013 09:01:41 +0000 The goal of this study was to investigate the influence of the brain-to-skull conductivity ratio (BSCR) on EEG source localization accuracy. In this study, we evaluated four BSCRs: 15, 20, 25, and 80, which were mainly discussed according to the literature. The scalp EEG signals were generated by BSCR-related forward computation for each cortical dipole source. Then, for each scalp EEG measurement, the source reconstruction was performed to identify the estimated dipole sources by the actual BSCR and the misspecified BSCRs. The estimated dipole sources were compared with the simulated dipole sources to evaluate EEG source localization accuracy. In the case of considering noise-free EEG measurements, the mean localization errors were approximately equal to zero when using actual BSCR. The misspecified BSCRs resulted in substantial localization errors which ranged from 2 to 16 mm. When considering noise-contaminated EEG measurements, the mean localization errors ranged from 8 to 18 mm despite the BSCRs used in the inverse calculation. The present results suggest that the localization accuracy is sensitive to the BSCR in EEG source reconstruction, and the source activity can be accurately localized when the actual BSCR and the EEG scalp signals with high signal-to-noise ratio (SNR) are used. Gang Wang and Doutian Ren Copyright © 2013 Gang Wang and Doutian Ren. All rights reserved. Viability Reduction and Rac1 Gene Downregulation of Heterogeneous Ex-Vivo Glioma Acute Slice Infected by the Oncolytic Newcastle Disease Virus Strain V4UPM Mon, 25 Mar 2013 17:21:05 +0000 Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer including glioma. Nevertheless, the capability of NDV infection on heterogeneous glioma tissue in a cerebrospinal fluid atmosphere has never been reported. Recently, Rac1 is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV. Rac1 is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression. Rac1 knockdown leads to significant inhibition of viral replication. In this work, we demonstrated that NDV treatment led to significant reduction of tumour tissue viability of freshly isolated heterogeneous human brain tumour slice, known as an ex vivo glioma acute slice (EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation of Rac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue. Zulkifli Mustafa, Hilda Shazana Shamsuddin, Aini Ideris, Rohaya Ibrahim, Hasnan Jaafar, Abdul Manaf Ali, and Jafri Malin Abdullah Copyright © 2013 Zulkifli Mustafa et al. All rights reserved. Electrophysiological Correlates of the Threshold to Detection of Passive Motion: An Investigation in Professional Volleyball Athletes with and without Atrophy of the Infraspinatus Muscle Mon, 14 Jan 2013 12:09:54 +0000 The goal of the present study is to compare the electrophysiological correlates of the threshold to detection of passive motion (TTDPM) among three groups: healthy individuals (control group), professional volleyball athletes with atrophy of the infraspinatus muscle on the dominant side, and athletes with no shoulder pathologies. More specifically, the study aims at assessing the effects of infraspinatus muscle atrophy on the cortical representation of the TTDPM. A proprioception testing device (PTD) was used to measure the TTDPM. The device passively moved the shoulder and participants were instructed to respond as soon as movement was detected (TTDPM) by pressing a button switch. Response latency was established as the delay between the stimulus (movement) and the response (button press). Electroencephalographic (EEG) and electromyographic (EMG) activities were recorded simultaneously. An analysis of variance (ANOVA) and subsequent post hoc tests indicated a significant difference in latency between the group of athletes without the atrophy when compared both to the group of athletes with the atrophy and to the control group. Furthermore, distinct patterns of cortical activity were observed in the three experimental groups. The results suggest that systematically trained motor abilities, as well as the atrophy of the infraspinatus muscle, change the cortical representation of the different stages of proprioceptive information processing and, ultimately, the cortical representation of the TTDPM. José Inácio Salles, Victor Rodrigues Amaral Cossich, Marcus Vinicius Amaral, Martim T. Monteiro, Maurício Cagy, Geraldo Motta, Bruna Velasques, Roberto Piedade, and Pedro Ribeiro Copyright © 2013 José Inácio Salles et al. All rights reserved. A Modified Technique for Culturing Primary Fetal Rat Cortical Neurons Tue, 23 Oct 2012 11:48:47 +0000 The study explored a modified primary culture system for fetal rat cortical neurons. Day E18 embryos from pregnant Sprague Dawley rats were microdissected under a stereoscope. To minimize enzymatic damage to the cultured neurons, we applied a sequential digestion protocol using papain and Dnase I. The resulting sifted cell suspension was seeded at a density of 50,000 cells per cm2 onto 0.1 mg/mL L-PLL-covered vessels. After a four-hour incubation in high-glucose Dulbecco’s Modified Eagle’s Medium (HG-DMEM) to allow the neurons to adhere, the media was changed to neurobasal medium that was refreshed by changing half of the volume after three days followed by a complete medium change every week. The cells displayed progressively robust neurite extension, and nonneuronal-like cells could barely be detected by five days in vitro (DIV); cell growth was still substantial at 14 DIV. Neurons were identified by -tubulin III immunofluorescence, and neuronal purity within the cultures was assessed at over 95% by both flow cytometry and by dark-field counting of -tubulin III-positive cells. These results suggest that the protocol was successful and that the high purity of neurons in this system could be used as the basis for generating various cell models of neurological disease. Sui-Yi Xu, Yong-Min Wu, Zhong Ji, Xiao-Ya Gao, and Su-Yue Pan Copyright © 2012 Sui-Yi Xu et al. All rights reserved. Expression of Neural Markers by Undifferentiated Rat Mesenchymal Stem Cells Tue, 09 Oct 2012 14:51:49 +0000 The spontaneous expression of neural markers by mesenchymal stem cells (MSCs) has been considered to be a demonstration of MSCs’ predisposition to differentiate towards neural lineages. In view of their application in cell therapy for neurodegenerative diseases, it is very important to deepen the knowledge about this distinctive biological property of MSCs. In this study, we evaluated the expression of neuronal and glial markers in undifferentiated rat MSCs (rMSCs) at different culture passages (from early to late). rMSCs spontaneously expressed neural markers depending on culture passage, and they were coexpressed or not with the neural progenitor marker nestin. In contrast, the number of rMSCs expressing mesengenic differentiation markers was very low or even completely absent. Moreover, rMSCs at late culture passages were not senescent cells and maintained the MSC immunophenotype. However, their differentiation capabilities were altered. In conclusion, our results support the concept of MSCs as multidifferentiated cells and suggest the existence of immature and mature neurally fated rMSC subpopulations. A possible correlation between specific MSC subpopulations and specific neural lineages could optimize the use of MSCs in cell transplantation therapy for the treatment of neurological diseases. Dana Foudah, Juliana Redondo, Cristina Caldara, Fabrizio Carini, Giovanni Tredici, and Mariarosaria Miloso Copyright © 2012 Dana Foudah et al. All rights reserved. Simulating Radiotherapy Effect in High-Grade Glioma by Using Diffusive Modeling and Brain Atlases Wed, 03 Oct 2012 09:55:55 +0000 Applying diffusive models for simulating the spatiotemporal change of concentration of tumour cells is a modern application of predictive oncology. Diffusive models are used for modelling glioblastoma, the most aggressive type of glioma. This paper presents the results of applying a linear quadratic model for simulating the effects of radiotherapy on an advanced diffusive glioma model. This diffusive model takes into consideration the heterogeneous velocity of glioma in gray and white matter and the anisotropic migration of tumor cells, which is facilitated along white fibers. This work uses normal brain atlases for extracting the proportions of white and gray matter and the diffusion tensors used for anisotropy. The paper also presents the results of applying this glioma model on real clinical datasets. Alexandros Roniotis, Kostas Marias, Vangelis Sakkalis, Georgios C. Manikis, and Michalis Zervakis Copyright © 2012 Alexandros Roniotis et al. All rights reserved. Identification of Physiologically Active Substances as Novel Ligands for MRGPRD Wed, 03 Oct 2012 09:30:02 +0000 Mas-related G-protein coupled receptor member D (MRGPRD) is a G protein-coupled receptor (GPCR) which belongs to the Mas-related GPCRs expressed in the dorsal root ganglia (DRG). In this study, we investigated two novel ligands in addition to beta-alanine: (1) beta-aminoisobutyric acid, a physiologically active substance, with which possible relation to tumors has been seen together with beta-alanine; (2) diethylstilbestrol, a synthetic estrogen hormone. In addition to the novel ligands, we found that transfection of MRGPRD leads fibroblast cells to form spheroids, which would be related to oncogenicity. To understand the MRGPRD novel character, oncogenicity, a large chemical library was screened in order to obtain MRGPRD antagonists to utilize in exploring the character. The antagonist in turn inhibited the spheroid proliferation that is dependent on MRGPRD signaling as well as MRGPRD signals activated by beta-alanine. The antagonist, a small-molecule compound we found in this study, is a potential anticancer agent. Makiko Uno, Satoko Nishimura, Keisuke Fukuchi, Yasuyuki Kaneta, Yoko Oda, Hironobu Komori, Shigeki Takeda, Tatsuya Haga, Toshinori Agatsuma, and Futoshi Nara Copyright © 2012 Makiko Uno et al. All rights reserved. Design of a 32-Channel EEG System for Brain Control Interface Applications Thu, 21 Jun 2012 15:20:56 +0000 This study integrates the hardware circuit design and the development support of the software interface to achieve a 32-channel EEG system for BCI applications. Since the EEG signals of human bodies are generally very weak, in addition to preventing noise interference, it also requires avoiding the waveform distortion as well as waveform offset and so on; therefore, the design of a preamplifier with high common-mode rejection ratio and high signal-to-noise ratio is very important. Moreover, the friction between the electrode pads and the skin as well as the design of dual power supply will generate DC bias which affects the measurement signals. For this reason, this study specially designs an improved single-power AC-coupled circuit, which effectively reduces the DC bias and improves the error caused by the effects of part errors. At the same time, the digital way is applied to design the adjustable amplification and filter function, which can design for different EEG frequency bands. For the analog circuit, a frequency band will be taken out through the filtering circuit and then the digital filtering design will be used to adjust the extracted frequency band for the target frequency band, combining with MATLAB to design man-machine interface for displaying brain wave. Finally the measured signals are compared to the traditional 32-channel EEG signals. In addition to meeting the IFCN standards, the system design also conducted measurement verification in the standard EEG isolation room in order to demonstrate the accuracy and reliability of this system design. Ching-Sung Wang Copyright © 2012 Ching-Sung Wang. All rights reserved. Neuroprotective Effect of Phosphocreatine on Focal Cerebral Ischemia-Reperfusion Injury Tue, 13 Mar 2012 10:22:18 +0000 Phosphocreatine (PCr) is a natural compound, which can donate high-energy phosphate group to ADP to synthesize ATP, even in the absence of oxygen and glucose. At present, it is widely used in cardiac and renal ischemia-reperfusion (IR) disease. In this study, to examine the protective efficacy of PCr against cerebral IR, disodium creatine phosphate was injected intravenously into rats before focal cerebral IR. Intracranial pressure (ICP), neurological score, cerebral infarction volume, and apoptotic neurons were observed. Expression of caspase-3 and aquaporin-4 (AQP4) was analyzed. Compared with IR group, rats pretreated with PCr had better neurologic score, less infarction volume, fewer ultrastructural histopathologic changes, reduced apoptosis, and lower aquaporin-4 level. In conclusion, PCr is neuroprotective after transient focal cerebral IR injury. Such a protection might be associated with apoptosis regulating proteins. Tiegang Li, Nana Wang, and Min Zhao Copyright © 2012 Tiegang Li et al. All rights reserved. A Window into the Heterogeneity of Human Cerebrospinal Fluid Aβ Peptides Tue, 23 Aug 2011 09:30:48 +0000 The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (Aβ) peptides leading to the formation of neurotoxic brain Aβ assemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF Aβ peptides. Specifically, we focused our attention on the heterogeneity of the CSF Aβ world discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating Aβ assemblies, and (3) communication modes for Aβ peptides and their microenvironment targets. Finally, we suggest that Aβ peptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function. Roberta Ghidoni, Anna Paterlini, Valentina Albertini, Elena Stoppani, Giuliano Binetti, Kjell Fuxe, Luisa Benussi, and Luigi F. Agnati Copyright © 2011 Roberta Ghidoni et al. All rights reserved. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain Mon, 20 Jun 2011 11:33:18 +0000 This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (𝑃<.05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway. Dong-Kyu Jang, Sang-In Park, Young-Min Han, Kyung-Sool Jang, Moon-Seo Park, Young-An Chung, Min-Wook Kim, Lee-So Maeng, Pil-Woo Huh, Do-Sung Yoo, and Seong-Whan Jung Copyright © 2011 Dong-Kyu Jang et al. All rights reserved. Treatment Pulse Application for Magnetic Stimulation Sun, 12 Jun 2011 10:30:36 +0000 Treatment and diagnosis can be made in difficult areas simply by changing the output pulse form of the magnetic stimulation device. However, there is a limitation in the range of treatments and diagnoses of a conventional sinusoidal stimulation treatment pulse because the intensity, width, and form of the pulse must be changed according to the lesion type. This paper reports a multidischarge method, where the stimulation coils were driven in sequence via multiple switching control. The limitation of the existing simple sinusoidal pulse form could be overcome by changing the intensity, width, and form of the pulse. In this study, a new sequential discharge method was proposed to freely alter the pulse width. The output characteristics of the stimulation treatment pulse were examined according to the trigger signal delay applied to the switch at each stage by applying a range of superposition pulses to the magnetic simulation device, which is widely used in industry and medicine. Sun-Seob Choi and Whi-Young Kim Copyright © 2011 Sun-Seob Choi and Whi-Young Kim. All rights reserved. Attenuation of Brain Nitrostative and Oxidative Damage by Brain Cooling during Experimental Traumatic Brain Injury Mon, 24 Jan 2011 12:55:09 +0000 The aim of the present study was to ascertain whether brain cooling causes attenuation of traumatic brain injury by reducing brain nitrostative and oxidative damage. Brain cooling was accomplished by infusion of 5 mL of 4°C saline over 5 minutes via the external jugular vein. Immediately after the onset of traumatic brain injury, rats were randomized into two groups and given 37°C or 4°C normal saline. Another group of rats were used as sham operated controls. Behavioral and biochemical assessments were conducted on 72 hours after brain injury or sham operation. As compared to those of the sham-operated controls, the 37°C saline-treated brain injured animals displayed motor deficits, higher cerebral contusion volume and incidence, higher oxidative damage (e.g., lower values of cerebral superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, but higher values of cerebral malondialdehyde), and higher nitrostative damage (e.g., higher values of neuronal nitric oxide synthase and 3-nitrotyrosine). All the motor deficits and brain nitrostative and oxidative damage were significantly reduced by retrograde perfusion of 4°C saline via the jugular vein. Our data suggest that brain cooling may improve the outcomes of traumatic brain injury in rats by reducing brain nitrostative and oxidative damage. Jinn-Rung Kuo, Chong-Jeh Lo, Ching-Ping Chang, Mao- Tsun Lin, and Chung-Ching Chio Copyright © 2011 Jinn-Rung Kuo et al. All rights reserved. Erratum of “Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies” Mon, 20 Sep 2010 15:34:35 +0000 Caroline Perronnet and Cyrille Vaillend Copyright © 2010 Caroline Perronnet and Cyrille Vaillend. All rights reserved. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration Sun, 27 Jun 2010 11:54:44 +0000 Neonatal blockade of N-methyl-D-aspartic acid (NMDA) receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF) expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND) 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC) were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia. Chunmei Guo, Yang Yang, Yun'ai Su, and Tianmei Si Copyright © 2010 Chunmei Guo et al. All rights reserved. Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies Thu, 17 Jun 2010 15:55:38 +0000 Two decades of molecular, cellular, and functional studies considerably increased our understanding of dystrophins function and unveiled the complex etiology of the cognitive deficits in Duchenne muscular dystrophy (DMD), which involves altered expression of several dystrophin-gene products in brain. Dystrophins are normally part of critical cytoskeleton-associated membrane-bound molecular scaffolds involved in the clustering of receptors, ion channels, and signaling proteins that contribute to synapse physiology and blood-brain barrier function. The utrophin gene also drives brain expression of several paralogs proteins, which cellular expression and biological roles remain to be elucidated. Here we review the structural and functional properties of dystrophins and utrophins in brain, the consequences of dystrophins loss-of-function as revealed by numerous studies in mouse models of DMD, and we discuss future challenges and putative therapeutic strategies that may compensate for the cognitive impairment in DMD based on experimental manipulation of dystrophins and/or utrophins brain expression. Caroline Perronnet and Cyrille Vaillend Copyright © 2010 Caroline Perronnet and Cyrille Vaillend. All rights reserved. Expressions of Neuregulin 1𝛽 and ErbB4 in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by Chronic MK-801 Administration Tue, 04 May 2010 16:19:21 +0000 Recent human genetic studies and postmortem brain examinations of schizophrenia patients strongly indicate that dysregulation of NRG1 and ErbB4 may be important pathogenic factors of schizophrenia. However, this hypothesis has not been validated and fully investigated in animal models of schizophrenia. In this study we quantitatively examined NRG1 and ErbB4 protein expressions by immunohistochemistry and Western blot in the brain of a rat schizophrenia model induced by chronic administration of MK-801 (a noncompetitive NMDA receptor antagonist). Our data showed that NRG1𝛽 and ErbB4 expressions were significantly increased in the rat prefrontal cortex and hippocampus but in different subregions. These findings suggest that altered expressions of NRG1 and ErbB4 might be attributed to the schizophrenia. Further study in the role and mechanism of NRG1 and ErbB4 may lead to better understanding of the pathophysiology for this disorder. Yu Feng, Xiao-Dong Wang, Chun-Mei Guo, Yang Yang, Ji-Tao Li, Yun-Ai Su, and Tian-Mei Si Copyright © 2010 Yu Feng et al. All rights reserved. Olfactory Ensheathing Glia: Drivers of Axonal Regeneration in the Central Nervous System? Mon, 01 Jan 1900 00:00:00 +0000 Olfactory ensheathing glia (OEG) accompany olfactory growing axons in their entry to the adult mammalian central nervous system (CNS). Due to this special characteristic, considerable attention has been focused on the possibility of using OEG for CNS regeneration. OEG present a large heterogeneity in culture with respect to their cellular morphology and expressed molecules. The specific characteristics of OEG responsible for their regenerative properties have to be defined. These properties probably result from the combination of several factors: molecular composition of the membrane (expressing adhesion molecules as PSA-NCAM, L1 and/or others) combined with their ability to reduce glial scarring and to accompany new growing axons into the host CNS. Their capacity to produce some neurotrophic factors might also account for their ability to produce CNS regeneration. M. Teresa Moreno-Flores, Javier Díaz-Nido, Francisco Wandosell, and Jesús Avila Copyright © 2002 Hindawi Publishing Corporation. All rights reserved. Automatic Discrimination of Abnormal Subjects Using the Visual Evoked Potential Spectral Components Mon, 01 Jan 1900 00:00:00 +0000 Study of visual evoked potential (VEP) is one of the utilized methods in clinical diagnosis of ophthalmology and neurological disorders. The automatic detection of VEP spectral components is an important tool in the diagnosis of mental activity. This paper presents a novel computational approach using feedforward neural network to identify abnormal subjects from changes in spectral components. The output vector from the feedforward neural network is based on the VEP spectral components. The software was developed to identify mental state from the VEP spectral components using Matlab software package. Using this approach, it is possible to perform real-time abnormality identification accurately on personal computers. R. Sivakumar and G. Ravindran Copyright © 2004 Hindawi Publishing Corporation. All rights reserved. Alzheimer Disease and Oxidative Stress Mon, 01 Jan 1900 00:00:00 +0000 Research in Alzheimer disease has recently demonstrated compelling evidence on the importance of oxidative processes in its pathogenesis. Cellular changes show that oxidative stress is an event that precedes the appearance of the hallmark pathologies of the disease, neurofibrillary tangles, and senile plaques. While it is still unclear what the initial source of the oxidative stress is in Alzheimer disease, it is likely that the process is highly dependent on redox-active transition metals such as iron and copper. Further investigation into the role that oxidative stress mechanisms seem to play in the pathogenesis of Alzheimer disease may lead to novel clinical interventions. George Perry, Adam D. Cash, and Mark A. Smith Copyright © 2002 Hindawi Publishing Corporation. All rights reserved.