Article 1: Effects of Transcranial Direct Current Stimulation at 1 Day Versus 1 Week After Cerebral Ischemia on Functional Improvement and Neuroplasticity in Rats

Objectives: To investigate whether transcranial direct current stimulation (tDCS) has the effects of functional improvement and neuroplasticity in cerebral ischemia, and to evaluate the optimal timing of tDCS. Design: Randomized, controlled study. Setting: Animal laboratory. Participants: Thirty Spague-Dawley rats randomly assigned to sham tDCS (ST, n=10), early tDCS (ET, n=10) or late tDCS (LT, n=10) group. Interventions: Rats of cerebral infarction were produced by 2 hours of middle cerebral artery occlusion (MCAO) followed by reperfusion. Anodal tDCS was applied at 1 day (EG) and 1 week (LS) after MCAO for 5 days. Main Outcome Measures: Barnes maze (BM), Rotarod (RR), Beam balance (BB), Motor behavioral index (MBI) were evaluated to assess the cognitive and motor function. Ischemic volumes were measured on T2-weighted brain magnetic resonance images. Immunohistochemistry with glial fibrillary acidic protein (GFAP), synaptophysin (Syn), growth associated protein 43 (GAP-43) and microtubule associated protein 2 (MAP-2) was used to detect neuroplasticity around ischemic lesion. Results: LT group had the significant increase in BB compared with ET and ST groups (P<.05). ET and LT groups significantly improved in BM and BMI with the comparison of ST group (P<.05). In RR, there was no significant difference among 3 groups. Ischemic lesion volumes did not differ significantly between groups. In immunohistochemistry, the number of GAP-43 and MAP-2 positive cell increased in LT group and slightly increased in ET group. But tDCS did not alter expression of GFAP and Syn staining. Conclusions: tDCS has more functional benefits after cerebral ischemia when applied at 1 week than 1 day after MCAO, and neuroplastistic effects against ischemic insult could be obtained.