Objective To assess the behavioral and synaptic plasticity effects of combining epidural cortical electrical stimulation with motor skills training following unilateral sensorimotor cortex (SMC)lesions in adult male rats.Methods Prior to lesion/electrode implantation surgeries, rats were pre-trained on the 'single pellet retrieval task' to a minimum criterion of 30％ success rate for two consecutive days. Then these rats received partial unilateral SMC lesions and implantation of electrodes over the remaining SMC. Fourteen days later, rats received daily reach training concurrent with anodal or cathodal 100 Hz or no stimulation for 14 days. Performance was measured as the percent of successes out of the total number of reach attempts [(total successes/total reach attempts)*100]. Conventional avidin biotinylated enzyme complex (ABC) immunohistochemical method was used quantify the expression and distribution of microtubule-associated protein 2 (MAP-2) and growth associated protein 43 (GAP-43) in motor cortical area underlying the electrode.Results There was no statistical significance between the two groups on the 14th day of preoperative training (P=0.546). The stimulation group had significantly greater rates of improvement with the impaired forelimb in comparison to control group (49.12％ vs 21.67％, P=0.004). The expression and distribution of MAP-2 and GAP-43 in the stimulating group were better than those in control group (GAP-43 : 0.3338 vs 0.3056. P=0.008; MAP-2: 0.4825 vs 0.4327. P=0.027).Conclusion These data indicate that cortical stimulation greatly improves the efficacy of rehabilitative reach training following SMC damage and raise the possibility that CS-induced functional improvements may be mediated by promoting the expression of MAP-2 and GAP-43 in perilesion cortex. and thus improve synaptic plasticity in cerebral ischemic rats.%目的 探讨皮层电刺激联合康复锻炼对大鼠局灶性脑缺血模型前肢运动功能恢复和运动区突触可垫性相关蛋白表达的作用.方法 选取成年健康雄性清洁级Sprague-Dawley(SD)大鼠20只.大鼠在"单粒食物摄取盒"中进行单柱食物小球抓取训练,持续2周,入选标准为连续2 d抓取成功率≥50%,记录术前锻炼第14天抓取食物小球的成功率.入选大鼠随机分为刺激组和对照组,每组6只,两组均行缺血造模和电极置入.参照大鼠脑立体定位图谱,将内皮素注射到大脑中动脉附近制作局灶性脑缺血模型,并在相应缺血区硬膜外放置刺激电极.电刺激从术后第14天开始,刺激组进行连续2周的电刺激和前肢功能锻炼,对照组只进行功能锻炼.记录刺激第14天两组大鼠抓取食物小球的成功率.取缺血侧运动区皮层按常规免疲组化抗生物素-生物素-过氧化酶法(avidin biotinylated enzyme complex,ABC)检测微管相关蛋白-2(microtubule-associated protein 2,MAp-2))和生长相关蛋白-45(growth associated protein 45,GAP-45)的表达和分布,采用病理图文分析系统进行图像分析.结果 两组大鼠术前"抓取成功率"差异无统计学意义(P=0.546).在电刺激第14天,刺激组大鼠的抓取成功率明显高于对照组大鼠(49.12%VS 21.67%,P=0.004).免疫组织化学结果显示刺激组大鼠脑缺血皮层运动区GAP-45和MAP-P的表达的光密度(optical density,OD)值比对照组明显增多(GAP-43:0.3338 vs 0.3056,P=0.008;MAP-2:0.4825 vs 0.4327,P=0.027).结论 皮层电刺激联合康复锻炼比单纯康复锻炼更能促进大鼠偏瘫前肢运动功能的恢复.提示皮层电刺激可能通过保护与改善大鼠脑缺血皮层周围运动区的突触超微结构,提高MAP-2和GAP-43的表达,促进脑缺血后突触可塑性的形成.
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