颅脑创伤（TBI）后神经炎症反应是继发性神经损伤的主要原因之一，而其发病机制至今尚未完全阐明。前期研究发现TBI后由HMGB1激活的脑微血管内皮细胞（BMEC）通过分泌富含miR-155的外泌体调控BMEC向促炎症功能状态转变，但BMEC源性外泌体miR-155调控TBI后神经炎症反应的作用机制尚不清楚。本课题将进一步明确由HMGB1激活的BMEC通过分泌富含miR-155的外泌体调控BMEC、炎性细胞（中性粒细胞和小胶质细胞）向促炎症功能状态转变；明确SHIP1为miR-155的直接作用靶点；在细胞和动物实验中验证由HMGB1激活的BMEC源性外泌体miR-155通过靶向SHIP1/NF-κB通路调控TBI后神经炎症反应。本研究成果将为TBI后神经炎症反应的调控机制提供崭新的认识，有望揭示BMEC源性外泌体及外泌体miR-155可能成为TBI后过度神经炎症反应的干预靶点。

Neuroinflammation is one of the leading causes of secondary neural injury following traumatic brain injury(TBI), and the pathogenesis has not been fully elucidated.Our previous study indicated that HMGB1-stimulated brain microvascular endothelial cell (BMEC) secreted miR-155 enriched exosome and exosomal miR-155 modulated the functional transition of BMEC itself to a pro-inflammatory state. So far, the role and mechanism of BMEC-derived exosome and exosomal miR-155 in neuroinflammation following TBI has not been clarified. We will further investigate whether HMGB1-stimulated BMEC-derived exosome and exosomal miRNA-155 modulates the functional transition of BMEC and inflammatory cells (neutrophil and microglia) to pro-inflammatory states. Next, we will verify SHIP1 as a direct target of miR-155. Finally, in vitro cell studies and TBI animal model studies, we will investigate whether HMGB1-stimulated BMEC-derived exosome and exosomal miRNA-155 activates neuroinflammation following TBI through targeting the SHIP1/NF-κB signaling pathway. Our findings may shed light on the pathogenesis of neuroinflammation following TBI and provide evidence supporting that BMEC-derived exosome and exosomal miRNA-155 may act as a promising intervention target of excessive neuroinflammation following TBI.