周围神经交叉移位治疗中枢性上肢瘫的运动中枢动态重塑模式研究

项目名称： 周围神经交叉移位治疗中枢性上肢瘫的运动中枢动态重塑模式研究

项目编号： No.81501945

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 蒋苏

作者单位： 复旦大学

项目金额： 16万元

中文摘要： 痉挛性偏瘫是中枢神经损伤后常见的严重后遗症，其中以上肢功能恢复最为困难。课题组原创性提出了通过周围神经交叉转位诱发脑功能重塑让健存半球控制瘫痪肢体的治疗策略，并获得了良好的临床效果。临床现象显示术后病人的运动功能从粗大动作到精细功能逐步改善，提示运动中枢的功能重塑是一个动态过程。但是，这种动态重塑规律尚不清楚。光遗传学技术具有皮层定位及刺激精确可控、可动态观察的优势。本课题拟在前期工作基础上，建立一侧脑外伤后经健侧颈七神经根移位的Thy1-ChR2-YFP转基因小鼠模型，应用在体光遗传学-电生理结合技术动态观察双侧上肢运动代表区兴奋参数的变化，结合行为学评估结果，阐明患肢运动功能恢复过程中运动中枢的脑功能重塑规律。研究成果对于今后采用皮层刺激等干预措施促进和加速有效的功能重塑有重要的理论价值。

中文关键词： 光遗传学；电生理；周围神经；皮层；可塑性变化

英文摘要： As one of the most serious sequelae of central nervous system injury, the results of treating upper extremity spastic paralysis are far from satisfactory. Original studies from our research group showed that changing the peripheral nerve pathway to increase the ipsilateral fibers in controlling the hemiplegia limb could achieve healthy cerebral hemisphere controlling bilateral upper extremities, and pretty good clinical results have also been achieved. However, the dynamic central plastic mechanism involved in limb functional recovery in the clinical patients’ consecutive recovery follow-ups is still not clear. Compared with other central intervening methods, the technique of optogenetics boasts of precise cortical localization and stimulation, repeatability as well as unreplaceable advantage of high efficiancy. Based on previous achievements, the project intends to innovatively apply in vivo optogenetic-electrophysiology coulped techniques to dynamically assess the plastic changes on the healthy hemisphere of Thy1-ChR2-YFP transgenic mice undergoing cross nerve transfer after traumatic brain injury, which can help dynamically follow up bilateral extremity representations and the motor cortex excitability parameter changes at different time intervals after surgery. Combined with behavioral assessment, the results will illustrate the central reorganizational changes during improved extremity function and helps to reveal the central cortical mechanism of unilateral hemisphere controlling bilateral extremities, providing basis for ensuing actively intervening cortical reorganization for a better recovery.

英文关键词： optogenetics;electrophysiology;peripheral nerve;cortical;plastic change