Review Article

Memory and Cognition-Related Neuroplasticity Enhancement by Transcranial Direct Current Stimulation in Rodents: A Systematic Review

Table 3

Role of transcranial direct current stimulation on neuroplasticity with a focus on animal models of neurotrauma.

AuthorYearAnimal modelSpecimen; genderStimulation parametersMain findings
Stimulation electrodeReference electrodeAnesthesiartDCS
PolarityPositionStimulation intensity (mA)Size (cm2)Stimulation duration (min)Current density (A/m2)PositionArea (cm2)

Nekhendzy et al. [97]2004Inflammatory nociception modelSprague Dawley rats; males31c-tDCSFrontal cortex2.25N/A45N/ABimastoidN/AYY (8 days)↓ Nociceptive response (effects lasted up to 50 min poststimulation)

Taib et al. [98]2009Left hemicerebellectomyWistar rats; males9a-tDCSRight or left motor cortex0.40.0712056.3Supraorbital region0.0064N/AY↑ T corticomuscular response amplitudes

Kim et al. [99]2010MCAOSprague Dawley rats; both genders61c-tDCS vs. a-tDCSLeft primary motor cortex (M1)0.10.78530N/ATrunk9YY (2 weeks)Neuroprotection over white matter and ischemic size ↓ (a-tDCS)
↑ Motor function

Jiang et al. [95]2012MCAOSprague Dawley rats; both genders90a-tDCS and c-tDCSMotor cortex0.10.785301.27Trunk9YY (daily, for 3, 7, or 14 days postlesion)↑ Motor function (7 and 14 days poststroke)
↑ Dendritic spine density
↓ PX1 expression (7th and 14 h day poststroke)

Yoon et al. [56]2012MCAOSprague Dawley rats; males30a-tDCSLeft primary motor cortex (M1)0.2N/A2028.2Anterior chest48.0YY (5 days stimulation 1 week vs. 1 day postischemia)↑ Motor function and Barnes maze performance (a-tDCS applied 1 week after ischemic injury)
↑ MAP-2 and GAP-43 expression around the perilesional area (a-tDCS applied 1 week postischemic injury)

Laste et al. [100]2012CFA injection/chronic inflammation inductionWistar rats; males18a-tDCSParietal cortex0.51.5 (ECG electrode)2033.4Supraorbital area1.5 (ECG electrode)NY (8 days)Significant differences in nociceptive response (immediately after and 24 h poststimulation)

Adachi et al. [101]2012CRSWistar rats; males48a-tDCSParietal cortex0.51.5 (ECG electrode)203.3Supraorbital area1.5 (ECG electrode)NY (8 days)↓ Nociceptive response in chronic stress condition
↓ TNF expression in the hippocampus

Peruzzotti-Jametti et al. [60]2013MCAOC57BL/6 mice; males137c-tDCS vs. a-tDCSLeft parietal cortex0.250.01444055Ventral thorax5.2N/AN (single session)↑ Infarct volume and ↑ BBB leakage (a-tDCS ipsilesional hemisphere)
Cortical Glu activity ↓, functional ↑ and ischemic damage ↓ (c-tDCS ipsilesional hemisphere)

Notturno et al. [102]2014MCAOSprague Dawley rats; both genders53c-tDCSLeft motor cortex0.20.0712028.6Ventral thorax10.5YN (single session)Ischemia volume ↓

Lu et al. [103]2015MPTP injectionC57bl mice; males36a-tDCSLeft frontal cortex0.20.0351057Between shoulders9N/AY (daily for 3 weeks)↑ Motor coordination (until 21 days poststimulation)
↑ TH and DA expression
↓ Oxidative stress

Spezia Adachi et al. [104]2015Restraint stress modelWistar rats; males78a-tDCSParietal cortex (midline)0.51.5 (ECG electrode)20N/ASupraorbital area1.5 (ECG electrode)NY (daily for 8 days)↓ Stress-induced nociceptive response
↑ Pain threshold
↓ BDNF levels (spinal cord and brainstem) in unstressed animals

Yoon et al. [31]2016Lateral fluid percussion methodSprague Dawley rats; males36a-tDCSHippocampus0.20.02252028.2Chest48 (corset)YY (daily for 5 days)↑ Perilesional area BDNF expression (tDCS 2 weeks post-TBI)
↑ Choline/creatinine ratios (tDCS 1 week post-TBI)
Motor performance recovery (2 weeks of tDCS)

Leffa et al. [33]2016SHRSHR rats and WKT rats; males48a-tDCSFrontal cortex0.51.52033.4Between ears1.5NY (8 consecutive days)↑ DA levels in STR in both rat strains and in the hippocampus following tDCS treatment in WKY
↑ BDNF levels in WKY rats

Liu et al. [105]2016PTISprague Dawley rats; N/A58c-tDCSRight S1FL2N/A2020.37VenterN/AN/AN (single session)Ischemia expansion inhibition (c-tDCS immediately postischemia induction)
↓ NeuN expression (c-tDCS+PSS group)

Braun et al. [106]2016MCAOWistar rats; males41c-tDCS vs. a-tDCSLeft primary motor cortex (M1)0.50.03515N/AVentral thoraxN/AYY (10-day stimulation; 5 days with 2-day interval)Gait recovery at day 16 poststroke (both polarities)
Faster recovery of limb strength (fully recovered strength at day 10 and gait at day 14 with c-tDCS)
↑ Microglia and neuroblasts in lesion ipsilateral cortex

Cioato et al. [107]2016Sciatic nerve chronic constrictionWistar rats; males84a-tDCS and c-tDCSParietal cortex (bicephalic)0.51.5 (ECG electrode)20N/ASupraorbital area1.5 (ECG electrode)NY (8 days)Nociceptive relieve (for up to 7 days poststimulation)
Reversion of T IL-1þ levels (48 h and 7 days poststimulation)

Filho et al. [108]2016Partial sciatic nerve compressionWistar rats; males144a-tDCSParietal cortex0.51.5 (ECG electrode)20N/ASupraorbital area1.5 (ECG electrode)NY (8 days)↓ BDNF expression (48 h poststimulation)
Reversion of behavioral alterations (analgesic and anxiolytic) associated with neuropathic pain

Moreira et al. [109]2016Pain and menopause (ovariectomised animals)Wistar rats; females45C-tDCSParietal cortex0.51.5 (ECG electrode)20N/ASupraorbital area1.5 (ECG electrode)NY (8 days)↓ Hypothalamic BDNF levels and T serum BDNF in ovariectomised animals

Dimov et al. [87]2016N/AWistar rats; males25c-tDCSLeft primary motor cortex (M1)0.250.022715N/AVentral thoraxN/ANN (single session)Bilateral ↓ Egr-1 expression in the PAG
Spinal ENK immunoreactivity ↓ in the DHSC

Liu et al. [110]2017PTISprague Dawley rats; males58c-tDCSS1FL2N/A20N/A3 mm lateral to lambdaN/AN/AN (single session)Prevention of ischemia injury expansion during hyperacute phase of ischemia (c-tDCS+PSS)

Kim & Han [111]2017Modified Tang’s method [128]Sprague Dawley rats; N/A31a-tDCSLeft motor cortex0.21300.26Ventral thorax9YNEarly recovery of consciousness and MEP and SEP prolonged latency (tDCS applied right after TBI)
↓ Astroglial GFAP immunoreactivity

Winkler et al. [112]2017Striatal 6-OHDA injectionSprague Dawley rats; females24a-tDCS and c-tDCSLeft motor cortexN/A0.16208Chest3NY (daily for 14 days)Graft survival, striatal dopaminergic reinnervation and motor recovery (a-tDCS)

de Souza et al. [113]2017PSNLSwiss mice; malesN/Aa-tDCS and c-tDCSParietal cortex (bicephalic)0.5N/A (EEG electrode)5; 10; 15; 20N/ASupraorbital areaN/A (EEG electrode)NN (single session)Antiallodynic effect (seen 4 h poststimulation of 15 min and 20 min)

Leffa et al. [46]2018ADHDSHR and WKY rats; males30a-tDCS (bicephalic)Frontal cortex (supraorbital area)0.51.5 (ECG electrode)2033.3Neck1.5 (ECG electrode)N/AY (8 days)↓ Inflammatory cytokines and reversion of long-term memory deficits in SHR rats

Paciello et al. [114]2018NIHLWistar rats; males124a-tDCSTemporal lobe (auditory cortex)0.350.06252056Ventral thorax12NY (2 days)↑ Dendritic spines density (layer 2/3 pyramidal neurons of the auditory cortex)
↑ BDNF and synaptophysin expression in auditory cortex (24 h poststimulation)

Fregni et al. [115]2018N/AWistar rats; males32N/AN/A (bicephalic)N/AN/A20N/AN/AN/AN/AY (8 days)tDCS prior to stress exposure prevented thermal hyperalgesia

Lee et al. [116]2019MPTP injectionC57bl mice; male60a-tDCSPrimary motor cortex (M1)N/AN/A30N/ABetween shouldersN/AN/AY (daily for 5 days)↑ Motor coordination
Rescue of MTPT-induced mitochondrial dysfunction (Ç ATP and GDH and $ Drp1 levels)

Callai et al. [117]2019CCI-IONWistar rats, males151a-tDCSParietal cortex (bicephalic)0.51.5 (ECG electrode)20N/ASupraorbital area1.5 (ECG electrode)NY (8 days)↓ Mechanical hyperalgesia
↓ TNF-a expression (7 days poststimulation)
↓ IL-10 (7 days poststimulation)
↓ LDH serum levels

Scarabelot et al. [118]2019CFA injection/chronic inflammation inductionSprague Dawley rats; males104a-tDCSParietal cortex (bicephalic)0.51.5 (ECG electrode)20N/ASupraorbital area1.5 (ECG electrode)N/AY (8 days)↓ Thermal and mechanical hyperalgesia
↑ IL-6 (in brainstem 24 h poststimulation)
↓ IL-10 (7 days poststimulation)
Normalization of BDNF levels (24 h poststimulation)

Abbreviations: rtDCS: repetitive transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; c-tDCS: cathodal transcranial direct current stimulation; C57BL/6: mouse strain; SHR: spontaneous hypertensive rats; WKY: Wistar Kyoto rats; ADHD: attention deficit hyperactivity disorder; 6-OHDA: 6-hydroxydopamine; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; TBI: traumatic brain injury; PTI: photothrombic ischemia; MCAO: middle cerebral artery occlusion; PSS: peripheral sensory stimulation; NIHL: noise-induced hearing loss; CC-ION: chronic constriction of the infraorbital nerve (pain model); PSNL: partial sciatic nerve ligation (pain model); CRS: chronic restraint stress (pain model); CFA: complete Freund’s adjuvant (pain model); BBB: blood–brain barrier; S1FL: forelimb region of the primary somatosensory cortex; M1: primary motor area; PAG: periaqueductal grey; DHSC: dorsal horn of the spinal cord; MEP: motor-evoked potentials; SEP: somatosensory evoked potentials; GFAP: glial fibrillary acidic protein; BDNF: brain-derived neurotrophic factor; Glu: glutamate NeuN: neuronal marker; PX1: pannexin 1; TH: thyroxine hydroxylase; Egr-1: early growth response protein 1; TNF: tumor necrosis factor; IL-1þ: interleukin 1 beta; IL-6: interleukin 6; IL-10: interleukin 10; LDH: lactate dehydrogenase enzyme; ATP: adenosine triphosphate; GDH: glutamate dehydrogenase; Drp1: dynamin-related protein; MAP-2: microtubule associated protein 2; GAP-43: growth associated protein 43; ENK: early embryo specific NK; DA: dopamine; ECG: electrocardiography; EEG: electroencephalogram; A/m2: ampere per square meter; mA: milliampere; cm2: square centimeter; min: minute; vs.: versus; Y: yes; N: no; N/A: not available.