颅脑创伤（TBI）相关凝血功能障碍（TBI-AC）发生和死亡率高，其发生机制尚不明确。课题组前期已发表的研究显示，小鼠TBI后脑源性微粒可释放进入循环血引起系统性凝血功能障碍。近期又证实，线粒体微粒（mtMP）占到了脑源性微粒的55%。其表面富含线粒体特异性磷脂—心磷脂，并具有高度促凝活性（Blood 2016）。mtMP同时也可以产生活性氧簇(ROS)并激活血小板从而介导凝血功能障碍。本课题拟借助小鼠TBI模型和扫描离子电导显微镜等细胞学技术，探索：1）TBI后产生的mtMP释放进入外周血的动态变化及其与血小板功能改变及凝血功能障碍的关系；2）mtMP与血小板结合的细胞学与分子生物学机制及其在TBI-AC中的作用；3）微粒清除蛋白Del-1对mtMP介导的TBI-AC的治疗作用，并初步探讨其分子机制。本项目旨在探索TBI后mtMP导致凝血功能障碍的机制，为TBI的防治提供新靶点。

Traumatic brain injury (TBI) is commonly associated with the inability of the blood to clot (coagulopathy), resulting in high mortality and mobility. The mechanism has not yet been defined. We have recently shown that a traumatically injured brain produces cellular microparticles that break down the brain-blood barrier and are released into systemic circulation. These brain-derived microparticles (BDMPs) are highly enriched in procoagulant anionic phospholipids and thrombin. We further show that intact or partially damaged mitochondrial microparticles (mtMPs) account for > 55% of BDMPs in the peripheral blood of mice subjected to acute TBI. These mtMPs expose the mitochondrial-specific phospholipid cardiolipin (CL), rendering them highly procoagulant. They also maintain their respiratory activity to generate reactive oxygen species that activate platelets to propagate coagulation and inflammation. We will use mouse models combined with in vitro experiments to further investigate: 1) The association of mtMPs released from traumatic brain and platelet disfunction and TBI-AC. 2) The molecular and cellular mechanism of the combation of mtMPs and platelet, and the roles of mtMPs in TBI-AC. 3) The mechanism of microparticles and apoptotic cell clearance protein Del-1 in mtMPs induced TBI-AC. These results will demonstrate a critical role of mtMPs in the development of coagulation abnormalities associated with TBI-AC and will provide a new therapeutic target for TBI.