Biodegradable controlled-release microsphere
systems made with the biocompatible
biodegradable polyester excipient poly [DL
lactide-co-glycolide] constitute an exciting new
technology for drug delivery to the central nervous
system (CNS). The present study describes
functional observations indicating that implantation
of dopamine (DA) microspheres encapsulated
within two different polymer excipients
into denervated- striatal tissue assures a
prolonged release of the transmitter in vivo.
Moreover, in this regard, the results show that
there were clear cut temporal differences in the
effect of the two DA microsphere formulations
compared in this study, probably reflecting variations
in the actual composition (i.e., lactide to
glycolide ratio) of the two copolymer excipients
examined. This technology has considerable potential
for basic research with possible clinical
application.

Amanda McRae

Stephan Hjorth

David W. Mason

Lynn Dillon

Thomas R. Tice

Microencapsulated Dopamine (DA)-Induced Restitution of Function in 6-OHDA-Denervated Rat Striatum in vivo: Comparison Between Two Microsphere Excipients

We report on the clinical status of 5 patients with Parkinson's disease (PD) 3 years after autologous adrenal medullary (AM)-to-caudate nucleus (CN) implanfion, and of 2 PD patients, 2 years after fetal ventral mesencephalon (VM)- and fetal adrenal (A)-to-CN homotransplantation. Current clinical evaluation of 4 of the AM grafted patients revealed sustained bilateral amelioration of their PD signs, most notably of rgidity, postural imbalance and gait disturbances, resulting in a substantial improvement in their quality of life. the disease-related dystonia of one of them disappeared only 2 years after surgery. The levodopa requirements of 2 of these patients and the anticholinergic therapy of another have been reduced. In agreement with the satisfactory clinical evaluation of these 4 patients, their neuropsychological and electrophysiological improvements, initially registered 3 months after surgery, have been maintained for 3 years. After 1 year of significant recovery, the 5th patient of this group has almost returned to her preoperative state.The 2 homotransplanted patients also showed sustained bilateral improvement of their PD signs. Two years after surgery, the most improved signs of the fetal VM case were rigidity, bradykinesia, postural imbalance, gait disturbances and facial expression. The fetal A case has only shown amelioration of rigidity and bradykinesia. Neither of them has shown significant neuropsychological changes. Their current levodopa requirements are less than before surgery.The improvements shown here by PD patients after brain tissue grafts go beyond those obtained using any other therapeutic approach, when levodopa fails. Although more studies and the development of these procedures are obviously required, these initial human trials appear to be resisting the test of time.

Ignacio Madrazo

Rebecca Franco-Bourland

Maricarmen Aguilera

Feggy Ostrosky-Solis

Mario Madrazo

Carlos Cuevas

Hugo Catrejon

Gabriel Guizar-Zahagun

Eduardo Magallon

Autologous Adrenal Medullary, Fetal Mesencephalic, and Fetal Adrenal Brain Transplantation in Parkinson's Disease: A Long-Term Postoperative Follow-Up

In the rat several paradigms of grafting of adrenal
medulla into the striatum were studied following the
induction of a parkinsonian model, using a unilateral
6-hydroxydopamine (6-OHDA) lesion of the substantia nigra
. Direct autologous grafting of adrenal medulla
into the caudate-putamen complex, a radiofrequency
lesion of the striatum alone, and a radiofrequency
lesion followed by delayed grafting of adrenal medulla
were compared by analyzing rotational behavior.
Direct grafting of adrenal medulla produced an
overall reduction in apomorphine induced turning
behavior by 43.5% when compared with controls.
Radiofrequency lesioning of the striatum without
graft showed the best improvement over control
animals with a 92% reduction in the total number of
rotations induced by apomorphine. Delayed grafting
into the caudate lesion cavity also produced a
dramatic reduction in motor asymmetry but did not
improve the behavioral outcome over that of the
lesion alone. Animals receiving only radiofrequency
lesions exhibited a band of increased tyrosine
hydroxylase like immunoreactivity bordering the
lesion cavity. Graft survival was limited in the nonlesioned
animals but appeared enhanced in the
animals whose striatum was previously lesioned.
Lesion location within the striatum influenced the
behavioral outcome. Large reductions in
apomorphine-induced rotations could result from
small lesions of the dorso-lateral striatum. These
findings indicate that selective destruction of the
caudate-putamen complex without tissue
transplantation produces a dramatic reduction in the
motor asymmetry of 6-OHDA treated rats. Suggested
explanations for the decrease in induced rotational
behavior with radiofrequency lesions include a
decrease in the number of striatal dopamine
receptors following cell destruction and lesioninduced
recovery of host dopaminergic afferents.
Striatal damage in critical areas can reverse some of
the motor behavior associated with the 6-OHDA
model and needs to be considered when evaluating
the effects of neural grafting in this model.

G. M. Friehs

R. G. Parker

L. S. He

S. J. Haines

D. A. Turner

T. J. Ebner

Lesioning of the Striatum Reverses Motor Asymmetry in the
6-Hydroxydopamine Rodent Model of Parkinsonism

Parallel morphological and electrophysiological studies of embryonic neocortical tissue (primordia of anterior parietal–presumptive sensorimotor–cortex) grafted into different regions of the host adult brain (sensori-motor cortex, caudate-putamen, septum or thalamus) were carried out to investigate to what extent the properties of transplanted embryonic neocortex–an advanced organizational form of neuronal tissue–are affected by homotopic or heterotopic surroundings.The results point to the importance of the host tissue environment as it influences both the size, the morphological and functional properties of the implanted embryonic cortical plate tissue. The cortical grafts were smaller in size when developed homo-topically in sensorimotor cortex and grew larger in heterotopic environment (caudate-putamen, septum, thalamus). The orientation of neuronal dendrites in the grafts tends to follow that seen in the surroundings. The homotopic grafts showed a better structural integration into the host brain. Differences were seen between intracortical and subcortical transplants in the spontaneous firing rate of neurons and in the ratio of units with various types of spontaneous discharge.

V. V. Senatorov

G. P. Obuhova

Z. Fülöp

Electrophysiological and Morphological Properties of Embryonic Neocortical Grafts Developing in Different Regions of the Host Rat Brain

Lesions of cortical areas 17 and 18 have been produced in newborn kittens by local injections of the excitotoxin ibotenic acid (ibo). Twenty-four hours after an injection on postnatal days 2 or 3, the gray matter of areas 17 and 18 near the center of the injection appears completely destroyed, with the exception of a one-to-two cell-thick layer at the bottom of layer I. Intact migrating neurons and radial glia can be found light- and electron-microscopically in the region affected. During the following weeks a several hundred micron thick cortex reforms. In the adult, this cortex consists of superficial layers I, II and III as proven by cytoarchitectonics, continuity with the corresponding layers of the normal cortex and cellular composition. We believe that the recovery is due to completion of migration by neurons spared by the ibo injection. More severe destruction of cerebral cortex, i.e. complete loss of the neuronal layers or their reduction to a few cell-thick mantles can be obtained with ibo injections at the end of the second or, respectively, first postnatal week. Severity of lesion also depends on the dose of ibo injected. There are interesting similarities between the ibo-injured cortex and two human neocortical displasias: microgyria and ulegyria.

G. M. Innocenti

P. Berbel

Analysis of an Experimental Cortical Network: i) Architectonics of Visual
Areas 17 and 18 After Neonatal Injections of Ibotenic Acid;
Similarities with Human Microgyria

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Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

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Chief Editor, Professor Baudry, is currently University Professor at Western University of Health Sciences in Pomona, CA. His research focuses on understanding the molecular/cellular mechanisms of learning and memory and neurodegeneration.

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Neural Plasticity - Table of contents 1991

title

Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

Neural Plasticity