丰富环境通过健侧皮层血流重建促进脑缺血损伤代偿机制的研究

Though it is crucial for recovery of central nervous system injury that establishment of compensation to ipsilateral limb via potential peripheral nerve from contralateral hemisphere, the mechanism is not clear. Our previous studies have found that enriched environment(EE, a condition providing multiple physical and social stimuli to animals) improved the overall functions of rats by increasing cerebral blood flow(CBF) in contralateral hemisphere. Thus, we will study the compensatory mechanism of brain from the perspective of blood supply. The remodelling of blood supply consists of structural and functional blood restoration. We will first explore the structural blood remodelling in contralateral hemisphere by laser speckle imaging method, and test the effects of VEGF-VEGFR-2 signal way in angiogenesis; then we will study functional blood remodeling by testing the reactivity of CBF in contralateral hemisphere when stimulating ipsilateral limb, and find out whether the vasodilative reactivity is caused by either Glu-iGluR or Glu-mGluR-5 signalling way by using microdialysis and Calcium imaging methods. Accordingly, we will demonstrate the effects of these two dimensional blood remodelling in post-ischemic compensation of contralateral hemisphere. And we therefore will provide a novel idea in the mechanism of EE and offer more evidences to supplement the rehabilitational theory of contralateral compensation.

单侧大脑损伤后，健侧大脑半球可通过功能区的重组代偿性地控制患肢，这是单侧脑缺血后肢体功能恢复的重要途径，但其机制尚未阐明。血流重建是功能区神经重组的前提。我们前期研究发现，丰富环境可以增加健侧皮层血流量从而促进患肢功能恢复，因而本课题拟将脑血流作为切入点，从基础血流重建和功能血流重建两方面来探寻大脑的代偿机制。首先，采用激光散斑检测健侧皮层的基础血流重建现象，运用免疫组化技术评估VEGF-VEGFR-2信号通路在该重建中的作用；然后，刺激患侧肢体，检测健侧皮层血流的实时反应来评估功能血流重建现象，运用微透析和钙离子成像技术检测神经血管偶联相关因子的动态变化，验证Glu-iGluR和Glu-mGluR-5信号通路在功能血流重建中的作用。最终，阐明健侧皮层基础和功能血流重建在脑缺血后功能代偿中的作用，为基础研究中丰富环境的作用机制提出一种新的观点，也为完善脑卒中康复的健侧代偿理论提供新的依据。

脑卒中是一种影响全球的医疗卫生问题，具有高发病率、高致残性等特点。康复治疗在脑卒中患者功能恢复中占有重要地位。单侧脑卒中后，大脑可通过其他功能脑区的重组代偿，改善功能障碍，这是单侧脑卒中后功能恢复的重要途径，但其机制尚未阐明。本课题组通过丰富环境康复干预，观察了其对于不同脑损伤模型的功能改善，并且进一步探讨了其对于不同脑区的组织水平、分子水平的具体机制。首先，采用激光散斑检测健侧皮层的基础血流重建现象，运用免疫组化技术评估VEGF相关信号通路在该重建中的作用；然后，刺激患侧胡须，检测健侧皮层血流的实时反应来评估功能血流重建现象，运用双光子成像技术检测神经血管偶联相关因子的动态变化，验证VEGF-PI3K-AKt-eNOS信号通路在功能血流重建中的作用。最终，阐明健侧皮层基础和功能血流重建在脑缺血后功能代偿中的作用。本课题组的研究成果为脑卒中康复治疗的健侧代偿理论提供新的依据，为进一步将丰富环境理念转化到临床脑卒中患者的康复治疗中提供了理论基础。相关成果是，发表SCI论文六篇，总影响因子18.912，中文论著一篇，培养五名博士生和一名博士后，获得四项科技奖项，顺利完成该课题各项任务。