颅脑外伤（TBI）会导致长期慢性神经功能障碍，其中小胶质细胞介导的慢性免疫炎症反应在这一过程中起主要作用。我们前期研究结果和文献报道表明，在中枢神经系统损伤后小胶质细胞可以向M1和M2方向极化而分别介导促炎和抑炎反应。IL-13作为一个小胶质细胞分泌的抑炎因子,在TBI中的作用机制并不十分明确。我们的预实验结果表明，外援性鼻饲给予IL-13能够减轻TBI所致的神经功能障碍，并且减少了TBI后中枢内M1型小胶质细胞数量而不改变M2小胶质细胞的表达。文献报道C/EBP信号通路参与IL-13介导LPS诱导M1小胶质细胞的死亡。因此本课题拟利用多种条件性敲除小鼠，结合免疫组织化学、分子生物学、行为学及电生理学等手段，解析IL-13如何促进TBI后的长期神经功能恢复，阐明IL-13促进M1型小胶质细胞死亡的分子机制，为临床治疗创伤性脑损伤提供更多的理论基础及潜在药物作用靶点。

Traumatic brain injury （TBI）leads to long-term chronic neural dysfunction. Chronic inflammation mediated by microglia plays an essential role in this process. Our recent studies showed that microglial cells could polarize to M1 or M2 phenotype to induce pro-inflammatory or anti-inflammatory responses, respectively, after central nervous system injuries. IL-13 is an anti-inflammatory cytokine secreted by microglia. The effect of IL-13 in TBI are not well understood. Our preliminary data showed that intranasal administration of IL-13 promoted the neurofunctional outcomes after TBI. Meanwhile, IL-13 reduced number of M1 phenotype microglia. It has been reported that C/EBP signal pathway was involves in LPS-induced microglial death mediated by IL-13. In this study, we will use conditional knockout mice combine with immunohistochemistry, molecular biological, behavioral and electrophysiology approaches to investigate the role of IL-13 in long-term functional rehabilitation after TBI and explore a mechanism involving C/EBP-mediated M1 phenotype microglia death in vivo and in vitro. This study will provide a novel therapeutic strategy and potential targets of drug development for the treatment of TBI.