线粒体跨细胞转移是细胞间交流方式之一，可能具有损伤修复作用。课题组前期发现，星形胶质细胞线粒体加入牵张损伤神经元培养液，可减轻细胞损伤。但创伤性脑损伤（TBI）后星形胶质细胞线粒体释放并转移至神经元及神经损伤修复作用和机制有待进一步阐明。我们推测：NAADP表达变化调控TBI后胶质细胞线粒体跨细胞转移至神经元，并促进神经功能改善。为验证此假说，本项目首先观察NAADP促进胶质细胞线粒体释放；利用CRISPR/Cas9质粒调控胶质细胞CD38水平，上调NAADP表达，细胞共培养条件下，增加线粒体跨细胞转移至神经元；构建GFAP标记的CD38腺相关病毒，立体定向注射转染小鼠海马胶质细胞，观察TBI后神经元及小鼠神经功能改变；最终分别从细胞、动物水平证实胶质细胞线粒体转移至受损神经元，促进神经损伤修复，及NAAD在其过程中的调控机制，为寻找TBI后神经损伤修复新的治疗靶点提供实验依据。

Intercellular mitochondria transfer roles in mediating communication between cells, which may play an important part in cell damage repair. We previously found that astrocyte-derived mitochondria alleviated impairments of neurons underwent stretch injury. The underline mechanisms of astrocytic mitochondria release and transfer in neuroprotection and neuroplasticity following traumatic brain injury (TBI) remains elusive, however. We postulated that post-traumatic neurons acquire astrocytic mitochondria via intercellular transfer, which ultimately promotes nerve repair and functional recovery. To verify this hypothesis, CD38 CRISPR activation plasmid was constructed to overexpress CD38 in astrocyte, and increase NAADP levels subsequently, also, the pre-sequence and reversecomplementary sequence of CD38 were confirmed and CD38 knockdown adeno-associated virus (AAV) with GFAP promoter were synthesized, specifically transfected mice astrocytes-hippocampal by stereotactic method to observe the changes of neurons and neurological functions in mice underwent TBI, our study aims to uncover mechanisms of astrocytic mitochondria transfer to injured neurons and nerve repair promotion, the regulatory effects of NAADP in vivo and in vitro. All these results will provide experimental basis for new treatment strategies in neurological function restoration after TBI.