Traumatic brain injury (TBI) induces inflammatory responses through microglial activation and polarization towards a more inflammatory state that contributes to the deleterious secondary brain injury. Glia maturation factor (GMF) is a pro-inflammatory protein that is responsible for neuroinflammation following insult to the brain, such as in TBI. We hypothesized that the absence of GMF in GMF-knockout (GMF-KO) mice would regulate microglial activation state and the M1/M2 phenotypes following TBI. We used the weight drop model of TBI in C57BL/6 mice wild-type (WT) and GMF-KO mice. Immunofluorescence staining, Western blot, and ELISA assays were performed to confirm TBI-induced histopathological and neuroinflammatory changes. Behavioral analysis was done to check motor coordination ability and cognitive function. We demonstrated that the deletion of GMF in GMF-KO mice significantly limited lesion volume, attenuated neuronal loss, inhibited gliosis, and activated microglia adopted predominantly anti-inflammatory (M2) phenotypes. Using an ELISA method, we found a gradual decrease in pro-inflammatory cytokines (TNF-α and IL-6) and upregulation of anti-inflammatory cytokines (IL-4 and IL-10) in GMF-KO mice compared with WT mice, thus, promoting the transition of microglia towards a more predominantly anti-inflammatory (M2) phenotype. GMF-KO mice showed significant improvement in motor ability, memory, and cognition. Overall, our results demonstrate that GMF deficiency regulates microglial polarization, which ameliorates neuronal injury and behavioral impairments following TBI in mice and concludes that GMF is a regulator of neuroinflammation and an ideal therapeutic target for the treatment of TBI.

颅脑外伤（TBI）通过小胶质细胞活化和极化作用诱导炎性反应，并朝着一种更炎性的状态转变，这种状态导致了有害的继发性脑损伤。胶质细胞成熟因子（GMF）是一种促炎蛋白，可引起脑部受伤（例如TBI）后的神经炎症。我们假设在GMF基因敲除（GMF-KO）小鼠中不存在GMF将调节TBI后小胶质细胞的激活状态和M1 / M2表型。我们在C57BL / 6小鼠野生型（WT）和GMF-KO小鼠中使用了TBI的体重减轻模型。进行了免疫荧光染色，蛋白质印迹和ELISA分析，以确认TBI诱导的组织病理学和神经炎性变化。进行行为分析以检查运动协调能力和认知功能。我们证明，GMF-KO小鼠中的GMF缺失显着限制了病变体积，减轻了神经元损失，抑制了神经胶质细胞增生，并且激活的小胶质细胞主要采用了抗炎（M2）表型。使用ELISA方法，我们发现与WT小鼠相比，GMF-KO小鼠的促炎性细胞因子（TNF-α和IL-6）逐渐降低，抗炎性细胞因子（IL-4和IL-10）上调，因此，促进小胶质细胞向更主要的抗炎（M2）表型过渡。GMF-KO小鼠显示出运动能力，记忆力和认知能力的显着改善。总体而言，我们的结果表明，GMF缺乏会调节小胶质细胞的极化，