颅脑创伤后血脑屏障继发性损伤机制及干预

项目名称： 颅脑创伤后血脑屏障继发性损伤机制及干预

项目编号： No.81330029

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 张建宁

作者单位： 天津医科大学

项目金额： 290万元

中文摘要： 创伤性脑损伤（TBI）致残及致死率高。TBI后免疫炎症反应及其所致的血脑屏障（BBB）继发性损伤机制尚不明确，这也是阻断继发性脑损伤救治TBI的关键环节。近年来本课题组在大量临床观察的基础上，对TBI后免疫炎症反应及其所致的继发性脑损伤进行了开创性研究，初步发现调节性T细胞、血管内皮细胞生长抑制因子（VEGI）和血管内皮细胞生长因子（VEGF）等多种免疫炎症相关细胞和细胞因子，以及内皮祖细胞与BBB继发性损伤与修复关系密切。本项目将借助小鼠脑创伤模型、体外BBB模型和临床病例观察进一步研究：1.TBI后BBB继发性损伤与免疫炎症相关因子的关系；2.VEGI/VEGF失衡在BBB继发性损伤中的作用机制及其意义；3.应用VEGI及VEGI转染的内皮祖细胞，探索防治BBB继发性损伤的新策略。通过研究深化对TBI后BBB继发性损伤机制的认识，为建立TBI后继发性脑损伤的临床治疗新方法奠定基础。

中文关键词： 颅脑创伤;血脑屏障;继发性脑损伤;神经炎症;神经免疫

英文摘要： Traumatic Brain Injury (TBI) has extremely high disability and mortality. The prevention of the secondary brain injury is crucial for the management of TBI. However the mechanisms responsible for the secondary insult on blood brain barrier (BBB) during TBI remain unknown. It is believed that inflammatory and immune ressponse elicited by TBI play a major role in the compromise of BBB. Based on extensive clinical observations, our group has investigated the inflammatory responses and secondary brain damage. Our recent observations implied that the repair of damaged BBB is closely related with endothelial progenitor cell (EPC), and proinflammatory cytokines, regulatory T cell, vascular endothelial growth inhibitor (VEGI), and vascular endothelial growth factor (VEGF). In this proposal, we will further investigate 1) the relationship between secondary damage of BBB following TBI and the inflammation mediators; 2) the role of VEGI/VEGF imbalance in inducing the secondary damage of BBB; 3) the novel clinical treatment strategy of secondary damage on BBB, such as VEGI and EPC transfected by VEGI. The outcome of this proposal will deepen the knowledge of the mechanism of secondary damage on BBB injury, and pave the way for defining the new clinical strategy of TBI.

英文关键词： traumatic brain injury;blood brain barrier;secondary brain injury;neuroinflammation;neuroimmune