神经损伤后瘫痪手运动功能恢复中皮质代表区定向“跃迁”的向导机制和脑可塑性研究

Limb paralysis following central and peripheral nervous injuries (e.g., stroke, brachial plexus injury) is a huge burden for the patients’ families as well as the society. Although the curing ability of acute stage has been greatly improved, the progress for chronic stage treatment is quite limited. Adaptive brain plasticity is acknowledged as an important mechanism for limb functional rehabilitation at the chronic stage. Based on the applicant’s previous study on peripheral nerve injury, the motor function recovery of the paralyzed limb was associated with the original location-oriented ‘shifting’ process of the new representation for the paralyzed hand. In the present study, phrenic nerve ‘end-to-end’ transfer, ‘end-to-side’ transfer and grafting surgeries are respectively performed in complete brachial plexus injury rats in different groups. We attempt to locate the ‘navigation area’ that potentially guide the oriented ‘shifting’ process. Functional MRI, micro-PET molecular imaging, multiple array of microelectrode mediated in vivo recording, cortico-cortical nerve tracing, and in vitro brain slices field potential recording techniques are used in the present study. The functional and structural connectivity between the navigation area and the restored motor representation was verified. Underlying synaptic plasticity and molecular mechanisms are also explored. The purpose of this study is to prepare theoretically for new interventions for improving hand motor function following nerve injuries. The new method will be based on the brain plasticity perspective of navigating an oriented shift of the new representation of the paralyzed hand to a proper location.

中枢和周围神经损伤（如脑卒中、臂丛神经损伤等）造成肢体瘫痪带给家庭和社会沉重负担，虽然急性期救治能力极大提高，但慢性后遗症期治疗进展缓慢。大脑良性重塑是慢性期患肢功能恢复的重要机制，申请人前期在周围神经损伤研究中发现瘫痪手的皮质代表区能否向原有代表区定向“跃迁”与患肢运动功能是否有效恢复密切相关。本课题分别建立臂丛神经损伤后膈神经端端移位、端侧移位和直接移植修复患肢屈肘功能的大鼠模型，联合运用小动物功能磁共振、Micro-PET分子显像、多通道微电极在体记录、脑区间神经示踪以及离体脑片场电位记录等技术，明确与患肢新生功能区向原有代表区定向“跃迁”有关的导航脑区，验证导航脑区间和新生功能区的功能和结构连接，阐明潜在突触可塑性机制和分子机制。为从脑重塑层面创新干预方法、诱导患肢功能区定向“跃迁”或者在异位大脑皮质重建、从而促进周围和中枢神经损伤后瘫痪手运动功能有效恢复奠定理论基础。

中枢和周围神经损伤（如脑卒中、臂丛神经损伤等）造成肢体瘫痪带给家庭和社会沉重负担，虽然急性期救治能力极大提高，但慢性后遗症期治疗进展缓慢。大脑良性重塑是慢性期患肢功能恢复的重要机制，申请人前期在周围神经损伤研究中发现瘫痪手的皮质代表区能否向原有代表区定向“跃迁”与患肢运动功能是否有效恢复密切相关。本课题分别建立臂丛神经损伤后膈神经端端移位、端侧移位和直接移植修复患肢屈肘功能的大鼠模型，联合运用小动物功能磁共振、Micro-PET显像、多通道微电极在体记录等技术，明确与患肢新生功能区向原有代表区定向“跃迁”有关的导航脑区，验证导航脑区间和新生功能区的功能和结构连接，阐明潜在突触可塑性机制和分子机制。为从脑重塑层面创新干预方法、诱导患肢功能区定向“跃迁”或者在异位大脑皮质重建、从而促进周围和中枢神经损伤后瘫痪手运动功能有效恢复奠定理论基础。