神经元线粒体损伤调控脑缺血过程中血脑屏障通透性的机制研究

项目名称： 神经元线粒体损伤调控脑缺血过程中血脑屏障通透性的机制研究

项目编号： No.81200928

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 戚智锋

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 血脑屏障(BBB)破坏是引起脑缺血继发水肿、出血的中心环节。脑缺血时神经元、星形胶质细胞及微血管内皮细胞作为神经血管单元的组成部分，均受到损害。以往的研究多侧重神经血管单元中单一因素对BBB的损伤，忽视了神经血管单元整体对BBB的调控。本课题将从神经元线粒体异常与BBB损伤的关系角度出发，以神经血管单元整体调控为重点，利用体外培养的BBB模型及大鼠脑缺血模型，探讨神经元线粒体损伤对BBB通透性的调控机制、该过程中神经血管单元各细胞类型间的相互作用，并探讨可能有效的干预措施。我们的假说是①脑缺血时神经元线粒体损伤可增加BBB通透性；②该过程可能由星形胶质细胞释放的血管内皮生长因子介导；③常压高浓度氧治疗可能通过抑制神经元线粒体损伤、下调星形胶质细胞中血管内皮生长因子水平，保护BBB功能。本研究将揭示脑缺血时神经元线粒体损伤调控BBB通透性的机制，为开发临床上可行的BBB保护措施提供实验基础。

中文关键词： 血脑屏障；脑缺血；神经血管单元；线粒体；

英文摘要： The blood-brain barrier (BBB) disruption is critical for edema and hemorrhage complications in cerebral ischemia. It is accepted that the coordinate responses in neurons, astrocytes and vascular endothelium, also called "neurovascular unit" (NVU), play an important role in stroke pathogenesis. However, early studies in BBB damage were mostly focused on the role of the single cell type in NVU, neglecting the integrative interaction in NVU to BBB permeability. In this project, we will use primary cultured NVU model and focal cerebral ischemic rat model to investigate the effects of mitochondria in ischemic neurons on BBB leakage and the cell-cell signaling in NVU during BBB injury. Moreover, normobaric hyperoxia (NBO) has been shown to maintain penumbral oxygenation, reduce infarction volumes and improve neurological function in animal stroke model. Here, we will also investigate the effects of NBO on BBB complications in NVU. According to the reports and our previous results, we hypothesize that the abnormal mitochondria in neurons may increase BBB permeability, mediated by increasing vascular endothelial growth factor (VEGF) in astrocytes. We also hypothesize that NBO may reduce BBB disruption by improving the mitochondria functions in neurons, depressing VEGF in astrocytes and may consequently decrease the comp

英文关键词： blood-brain barrier；cerebral ischemia；neurovascular unit；mitochondria；