脑缺血是严重影响人类生命健康的疾病。线粒体是具有高度动态性的细胞器，呈现"分裂-融合"的动态变化；其在神经元损伤过程中的关键作用已被认识。在培养细胞的病理模型中检测到线粒体的片段化，并有证据显示其片段化引发细胞损伤。然而，神经元的线粒体在在体缺血条件下的行为尚无研究，对线粒体"分裂-融合"动态的调控机制及其影响神经元命运的机制则更缺乏认识。本研究拟利用给培养神经元以氧糖剥夺的离体缺血模型及在双光子显微镜下造成光化学血栓形成的在体局部微中风模型，系统观测线粒体形态动态变化，并多角度研究线粒体形态变化对其功能的影响；利用第二代深度测序技术结合生物信息学分析，筛选出调控Drp1、Fis1、Opa1等线粒体形态动态变化相关蛋白的miRNA；离体、在体敲减所筛选的miRNA，研究其对神经元线粒体形态变化及对神经元存活的影响，并在在体缺血模型下检测其保护作用。研究结果将为脑卒中等疾病的治疗提供新策略。

Stroke is a leading cause of death and disability. Mitochondria play very important roles both in health and disease. Mitochondria are highly dynamic cell organelles which exhibit "fission and fusion" dynamics. Mitochondrial fragmentation was observed in some pathological models of cultured cells which was suggested to induce cell damage. However, their behavior in the in vivo ischemic model is totally unknown. Furthermore, the mechanisms underlying the "fission and fusion" dynamics regulation and their effects on neuronal viability remain poorly understood. Using two-photon microscope, we will real time record the changes of neuronal mitochondrial morphology, and their membrane potential, super oxygen radical production in the in vivo photothrombosis ischemia model. Then the effect of mitochondrial "fission and fusion" dynamics on their physiological function and neuronal viability will be determined. By combined analysis of second-generation sequencing and bioinformatics, we will screen the microRNAs, which regulate the mitochondrial morphological dynamics, as a target to manipulate mitochondria. Furthermore, by cerebral delivery of miRNA mimics and miRNA antagomirs of screened miRNA, we will determine the effects of the miRNA on neuronal damage in the middle cerebral artery occlusion model. Not only will our work solve a basic scientific problem, but also probably provide a new therapeutic strategy or target for stroke.