星形胶质细胞激活在创伤性脑损伤（TBI）发病中发挥关键作用。我们前期在GMFB基因敲除斑马鱼/小鼠TBI模型中发现，GMFB是TBI后星形细胞胶质化激活的必要条件；GMFB表达于创伤部位小胶质细胞和星形胶质细胞；在小胶质细胞中，GMFB促进小胶质细胞炎症性激活；在星形胶质细胞中，GMFB促进星形细胞胶质化关键转录因子STAT3激活，而GMFB/STAT3信号轴促进LCN2生成和分泌，LCN2已知可促进小胶质细胞和星形胶质细胞激活。由此推测，GMFB可能通过内源性和外源性途径促进TBI后星形胶质细胞激活。我们拟通过原代细胞培养、立体定向注射等体内外方法，研究GMFB在调控TBI后小胶质细胞和星形胶质细胞相继激活中的作用、星形胶质细胞中GMFB-STAT3-LCN2轴激活的机制、LCN2是否激活小胶质细胞/星形胶质细胞。本项目的完成将进一步揭示TBI后星形胶质细胞激活的重要机制。

Astrocyte activation plays a key role in the pathogenesis of traumatic brain injury (TBI). We previously found in the zebrafish/mouse TBI model with GMFB gene knockout that GMFB is necessary for the activation of astrocyte after TBI. GMFB was expressed in microglia and astrocytes at the site of trauma. In microglia, GMFB promotes inflammatory activation of microglia. In astrocytes, GMFB promotes the activation of STAT3, a key transcription factor for astrogliosis. GMFB/STAT3 signaling axis promotes the production and secretion of LCN2, which is known to promote the activation of microglia and astrocytes. Therefore, GMFB may promote the activation of astrocytes after TBI through endogenous and exogenous pathways. We intend to study the role of GMFB in the subsequent activation of microglia and astrocytes after TBI, the activation mechanism of GMFB-STAT3-LCN2 axis in astrocytes, and whether LCN2 activates microglias/astrocytes. In vivo and in vitro methods such as primary cell culture and Stereotactic injection are used. The completion of this project will further reveal the important mechanism of astrocyte activation after TBI.