颅脑创伤后的血脑屏障损害是颅脑创伤后继发性病理改变的关键环节。低温治疗可以保护血脑屏障功能，但其分子机制尚未被阐明。作为血脑屏障重要组成部分之一的脑血管周细胞（pericyte）在血脑屏障生理功能与病理改变中均发挥重要作用。结合前期研究与预实验结果，本课题组提出假设：低温治疗通过迁移相关通路调控颅脑创伤后血管周细胞迁移特性，起到保护血脑屏障功能的作用。本项目拟通过建立小鼠控制性脑皮质损伤模型及周细胞机械损伤模型，研究脑血管周细胞在颅脑创伤及低温后形态和迁移特性的改变,并探索低温对颅脑创伤后血管周细胞迁移相关uPA-uPAR-MMP9及下游通路的影响。通过特异性抑制剂、siRNA以及腺相关病毒下调uPA-uPAR-MMP9及下游通路，揭示其在颅脑创伤低温后调节脑血管周细胞的迁移特性以及血脑屏障功能中的作用,从而阐明低温改善血脑屏障功能的关键分子机制，并为颅脑创伤治疗提供新思路。

The disruption of the blood-brain barrier (BBB) plays a key role in the pathological changes after traumatic brain injury (TBI). It is found that hypothermia therapy can protect the permeability of BBB and alleviate brain edema. However, its mechanism still remains to be elucidated. Since pericyte is known as a crucial component of BBB, this project aims to explore the effect of hypothermia on pericyte morphology and migration after TBI using pericyte strain-induced injury model and mice controlled cortical injury model. This project also aims to illustrate the changes in the expression level of the migration-related pathway, uPA-uPAR-MMP9 and its downstream pathways, after post-TBI hypothermia. Specific inhibitor, siRNA and specific promotor adeno-associated virus are applied to downregulate the uPA-uPAR-MMP9 and its downstream pathways thus exploring the role of these pathways in pericytes migration and BBB function following post-TBI hypothermia therapy. Hopefully, this project will reveal the key mechanism of hypothermia in protecting BBB function and provide new therapeutic approaches.