›› 2011, Vol. 6 ›› Issue (05): 388-394.

• 论著 • 上一篇    下一篇

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及运动区突触可塑性相关蛋白表达的影响

郑建1,杨力军1,谢瑞禄1,赵兰峰2,薛晓伟3,王硕1,赵继宗1,曹勇1   

  1. 1北京市首都医科大学附属北京天坛医院神经外科2首都医科大学疼痛生物研究所3首都医科大学病生教研室
  • 收稿日期:2010-08-30 修回日期:2010-08-30 出版日期:2011-05-20 发布日期:2011-05-20
  • 通讯作者: 曹勇

Cortical electrical stimulation combined with rehabilitative training enhance forelimb motorfunction and synaptic plasticity following focal cortical ischemia in rats

ZHENG Jian, YAGNLi-Jun, XIE Rui-Lu, et al

  

  • Received:2010-08-30 Revised:2010-08-30 Online:2011-05-20 Published:2011-05-20

摘要: 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塑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”中进行单粒食物小球抓取训练,持续2周,入选标准为连续2 d抓取成功率≥30%,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疫组化抗生物素-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-43(growth associatedprotein 43,GAP-43)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-43和MAP-2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。

关键词: 脑缺血; 经皮神经电刺激; 康复; 神经元可塑性; 微管相关蛋白质; GAP-43蛋白

Abstract: Objective To assess the behavioral and synaptic plasticity effects of combining epidural corticalelectrical 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 ‘singlepellet retrieval task’ to a minimum criterion of 30% success rate for two consecutive days. Thenthese rats received partial unilateral SMC lesions and implantation of electrodes over the remainingSMC. Fourteen days later, rats received daily reach training concurrent with anodal or cathodal100 Hz or no stimulation for 14 days. Performance was measured as the percent of successes outof the total number of reach attempts [(total successes/total reach attempts)*100]. Conventionalavidin biotinylated enzyme complex (ABC) immunohistochemical method was used quantify theexpression and distribution of microtubule-associated protein 2 (MAP-2) and growth associatedprotein 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 preoperativetraining (P=0.546). The stimulation group had significantly greater rates of improvementwith the impaired forelimb in comparison to control group (49.12% vs 21.67%, P =0.004). Theexpression and distribution of MAP-2 and GAP-43 in the stimulating group were better than thosein 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 ofrehabilitative reach training following SMC damage and raise the possibility that CS-inducedfunctional improvements may be mediated by promoting the expression of MAP-2 and GAP-43 inperilesion cortex, and thus improve synaptic plasticity in cerebral ischemic rats.

Key words: Brain ischemia; Transcutaneous electric nerve stimulation; Rehabilitation; Neuronal plasticity; Microtubule-associated proteins; GAP-43 protein