小胶质细胞的CD200/CD200R通路在脑缺血后功能重建中对突触可塑性和神经发生的影响及机制研究

Stroke is a leading cause of long-term neurological disability, with many patients experiencing persistent cognitive, motor, sensory impairments. Rehabilitation therapy is the most effective way to decrease disability after stroke. However, rational scheme and mechanism of stroke rehabilitation therapy is unclear. Remodeling of ischemic brain tissue involves interactions between neurons, glial and microvascular cells that create a microenvironment in which neurological recovery may ensue. Mount evidence has demonstrated that microglia play an important role on stroke by regulating neuroinflammation. In brain developmental stages microglia contribute to the synaptic plasticity and neurogenesis. CD200/CD200R signaling pathway mediates the cross-talk between neuron and microglia. However, the brain microenvironment of post-stroke is the similar to the brain developmental microenvironment. Our hypothesis is that microglia will contribute synaptic plasticity and neurogenesis in post-stroke function recovery via CD200/CD200R signaling pathway.. In brief, we will explore the effects of microglia on synaptic plasticity and neurogenesis via CD200/Cd200R signaling pathway after treadmill training in post-stroke by use of various technological methods. Our study will mainly focus on three aspects: (1).the effects of treadmill training after stroke on the animal motor, sensor and cognitive function； (2). the effects of treadmill training after stroke on microglia behavior; (3).the effects of microglia after treadmill training in post-stroke on synaptic plasticity and neurogenesis and the possible mechanism of CD200/CD200R signaling pathway involves in the above pathological process. This study may help us find a new way to improve neuroplasticity and functional reconstruction, and the CD200/CD200R signaling pathway would provide a new potential target for develop optimal rehabilitation therapy strategies for promoting stroke recovery.

脑卒中后康复是目前临床迫切需要解决的课题，也是降低脑卒中后致残率最有效方法。介导小胶质细胞与神经元之间相互作用的CD200/CD200R信号通路在突触可塑性和神经发生中发挥重要的作用，而突触可塑性和神经发生在缺血后功能重建中扮演重要角色，所以CD200/CD200R信号通路在脑缺血后功能重建中可能起着重要作用，但相关研究国内外尚无报道。本课题将从分子、细胞和整体动物等多层面，探讨小胶质细胞的CD200/CD200R通路在脑缺血后功能重建中对突触可塑性和神经发生的影响及机制。内容包括脑缺血后康复期运动训练后动物运动、感觉和认知的改变；小胶质细胞行为的改变；小胶质细胞对突触可塑性和神经发生的影响及CD200/CD200R通路参与以上过程的机制。课题的完成将找到可促进神经可塑和功能重建的有效途径，为今后以CD200/CD200R通路为靶点促脑卒中康复的药物开发和临床促脑卒中康复提供新思路和手段。

脑卒中后康复是目前临床迫切需要解决的课题，也是降低脑卒中后致残率最有效方法。介导小胶质细胞与神经元之间相互作用的CD200/CD200R信号通路在突触可塑性和神经发生中发挥重要的作用，而突触可塑性和神经发生在缺血后功能重建中扮演重要角色，所以CD200/CD200R信号通路在脑缺血后功能重建中可能起着重要作用。本课题从分子、细胞和整体动物等多层面，探讨小胶质细胞的CD200/CD200R通路在脑缺血后功能重建中对突触可塑性和神经发生的影响及机制。经过4年的研究，研究发现：（1）脑缺血后运动训练可显著改善缺血大鼠的运动、感觉和认知功能；（2）激活或抑制CD200/CD200R通路，可以促进或降低大鼠脑缺血后运动训练导致的神经发生，并且促进或降低脑缺血后的功能改善；（3）激活或抑制CD200/CD200R通路，还可以增强或减弱大鼠脑缺血后运动训练导致的突触可塑性的改变。并且促进或降低脑缺血后的功能改善；（4）大鼠脑缺血后CD200Fc片段单独可以促进或增强运动训练引起的运动、感觉和认知功能的改善。总之，小胶质细胞 CD200/CD200R 通路参与脑缺血后运动训练对大鼠运动、感觉和认知功能的影响，激活该通路有利于促进脑缺血后大鼠的功能康复。该课题从小胶质细胞 CD200/CD200R 通路的角度，阐明了运动训练促进脑缺血后功能恢复的机制，为以后针对 CD200/CD200R通路为靶点的药物开发和临床治疗中风提供新的思路。本课题共发表14篇文章，7篇SCI，7篇核心期刊，影响因子累计有37。课题组参加1次国际会议，2次国内学术会议，会议论文有3篇。期间培养硕士研究生4名，博士研究生2名。课题期间有1名研究生获得国家学业奖学金。