物理干预有特殊的生物学效应，如低温的神经保护作用、直流电场的诱导细胞定向迁移及创伤修复作用。基于小胶质细胞（MG）参与颅脑创伤后的炎症反应并有神经保护和损伤的双向作用，结合前期预实验初步发现（低温、电场干预可调控小胶质细胞M1/M2型比例，调控细胞运动能力和迁移方向），我们推测：低温和电场干预能通过一定的分子机制，调控MG表型转变并诱导细胞定向迁移，协调发挥神经保护作用。本研究将通过体外细胞实验，研究低温及电场干预对MG功能的影响、相关分子机制；其次构建小鼠控制性皮层损伤模型，从动物在体水平研究物理干预的神经保护作用，尤其是Gas5信号通路（Gas5-miR-103-PTEN/LRRK2）对MG功能的影响；最后，明确低温及电场干预对人源性MG功能、趋电运动特性的影响。该项研究将为低温和电场单独或联合应用于神经保护提供理论依据，为颅脑创伤提供新的治疗策略。

Physical intervention has specific biological effects, such as hypothermic neuroprotection, direct current electric field (EF) guided cell directional migration and wound healing. Microglia (MG) is dramatically involved in the inflammatory process following traumatic brain injury (TBI), which functioning on both neuroprotection and neuro-deterioration. Together with the findings from our pilot experiment (hypothermia and/or EF regulates the phenotypic transformation of M1/ M2 of MG, modulates cell motility and directional migration), we speculate that hypothermia and/or EF may regulate phenotypic transformation of MG, induce MG directional migration, and function as neuroprotection via certain molecular mechanism. In this study we intend to explore the biological effects and mechanism of hypothermia and EF on microglia in vitro. We will then explore the neuroprotection of physical intervention in vivo through a controlled cortex injury model, and verify the effect of Gas5 signaling pathway (Gas5-miR-103-PTEN/ LRRK2) in MG. We will finally examine the biological effects of hypothermia and applied EF on human-derived microglia. This study will provide fundamental evidence for the hypothermia and EF application (individually or jointly) in neuroprotection. Novel treatment strategy for TBI will possibly be developed gradually.