Comorbid post-traumatic stress disorder with traumatic brain injury (TBI) produce more severe affective and cognitive deficits than PTSD or TBI alone. Both PTSD and TBI produce long-lasting neuroinflammation, which may be a key underlying mechanism of the deficits observed in co-morbid TBI/PTSD. We developed a model of co-morbid TBI/PTSD by combining the closed head (CHI) model of TBI with the chronic variable stress (CVS) model of PTSD and examined multiple behavioral and neuroinflammatory outcomes. Male C57/Bl6 mice received sham treatment, CHI, CVS, CHI then CVS (CHI → CVS) or CVS then CHI (CVS → CHI). The CVS → CHI group had deficits in Barnes maze or active place avoidance not seen in the other groups. The CVS → CHI, CVS and CHI → CVS groups displayed increased basal anxiety level, based on performance on elevated plus maze. The CVS → CHI had impaired performance on Barnes Maze, and Active Place Avoidance. These performance deficits were strongly correlated with increased hippocampal Iba-1 level an indication of activated MP/MG. These data suggest that greater cognitive deficits in the CVS → CHI group were due to increased inflammation. The increased deficits and neuroinflammation in the CVS → CHI group suggest that the order by which a subject experiences TBI and PTSD is a major determinant of the outcome of brain injury in co-morbid TBI/PTSD.

合并创伤性脑损伤 (TBI) 的创伤后应激障碍比单独的 PTSD 或 TBI 产生更严重的情感和认知缺陷。PTSD 和 TBI 都会产生持久的神经炎症，这可能是共病 TBI/PTSD 中观察到的缺陷的关键潜在机制。我们通过将 TBI 的闭合头 (CHI) 模型与 PTSD 的慢性可变应激 (CVS) 模型相结合，开发了一种共病 TBI/PTSD 模型，并检查了多种行为和神经炎症结果。雄性C57/Bl6小鼠接受假处理，CHI、CVS、CHI然后CVS（CHI→CVS）或CVS然后CHI（CVS→CHI）。CVS → CHI 组在巴恩斯迷宫或活动场所回避方面存在其他组中未见的缺陷。根据高架十字迷宫的表现，CVS → CHI、CVS 和 CHI → CVS 组的基础焦虑水平有所增加。CVS → CHI 在巴恩斯迷宫和活动场所回避方面的表现受损。这些表现缺陷与海马 Iba-1 水平升高密切相关，这是激活 MP/MG 的标志。这些数据表明，CVS→CHI 组中更大的认知缺陷是由于炎症增加所致。CVS → CHI 组的缺陷和神经炎症增加表明，受试者经历 TBI 和 PTSD 的顺序是共病 TBI/PTSD 脑损伤结果的主要决定因素。