脑中风后小胶质细胞增生的功能及调控机制

项目名称： 脑中风后小胶质细胞增生的功能及调控机制

项目编号： No.31471045

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 张胜祥

作者单位： 兰州大学

项目金额： 88万元

中文摘要： 小胶质细胞是脑内具有免疫活性的细胞，在正常的脑组织中，小胶质细胞处于静息态,对周围的组织起着监测和保护作用。脑中风后，小胶质细胞被迅速激活并在缺血损伤区周围增生，目前对脑中风后小胶质细胞增生的功能还有很大争议，小胶质细胞增生的调控机制也尚不清楚。本项研究拟利用可选择性杀死小胶质细胞的转基因荧光小鼠建立中风模型，采用活体内双光子荧光显微成像技术、免疫组织化学染色和行为学测试等研究方法，确定脑中风后不同时间点小胶质细胞的增生对缺血半影区神经元突触结构、脑梗死体积以及动物行为恢复的影响。此外，我们拟结合活体成像观察和细胞培养的方法，探讨影响小胶质细胞增生的主要因素和信号调控机制。本研究结果可为中风的治疗提供新的思路和理论依据。

中文关键词： 中风；小胶质细胞；小胶质细胞增生；调控机制；双光子成像技术

英文摘要： Microglia are immunocompetent cells in the brain. In the normal brain, microglia are in resting state and have important roles in the surveillance, support and protection of tissue integrity. Microglia are rapidly acticvated and proliferate surrounding the lesion site after ischemic stroke. However, the functions of microgliosis after ischemic stroke are controversial, and the regulatory mechanisms of microgliosis remain largely unclear. In this study, we will investigate the effects of microgliosis on synaptic structures in ischemic penumbra, infarct volume and behavioral recovery at different time points after ischemic stroke. A photothrombosis stroke model will be established in transgenic fluorescent mice that allow for specific depletion of microglia, and in vivo two-photon imaging, immunohistochemistry and behavioral analysis will be used to determine the functions of microgliosis. In addition, we will determine the major factors and regulatory mechanisms of microgliosis after ischemic stroke by combining in vivo imaging and cell culture model system. Results of this study will provide new insights and theoretical evidence for therapeutic treatments of ischemic stroke.

英文关键词： Stroke;Microglia;Microgliosis;Regulatory mechanisms;Two-photon imaging