Fesharaki-Zadeh Arman, Miyauchi Jeremy T, St Laurent-Arriot Karrah, Tsirka Stella E, Bergold Peter J
Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, New York.
Department of Physiology, State University of New York, Downstate Medical Center, Brooklyn, New York.
ASN Neuro. 2020 Jan-Dec;12:1759091420979567. doi: 10.1177/1759091420979567.
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.
创伤性脑损伤（TBI）合并创伤后应激障碍（PTSD）所产生的情感和认知缺陷比单独的PTSD或TBI更为严重。PTSD和TBI都会引发持久的神经炎症，这可能是TBI/PTSD共病中所观察到的缺陷的关键潜在机制。我们通过将TBI的闭合性颅脑损伤（CHI）模型与PTSD的慢性可变应激（CVS）模型相结合，建立了TBI/PTSD共病模型，并研究了多种行为和神经炎症结果。雄性C57/Bl6小鼠接受假手术治疗、CHI、CVS、先CHI后CVS（CHI→CVS）或先CVS后CHI（CVS→CHI）。CVS→CHI组在巴恩斯迷宫或主动位置回避任务中存在其他组未出现的缺陷。基于高架十字迷宫的表现，CVS→CHI组、CVS组和CHI→CVS组的基础焦虑水平均有所升高。CVS→CHI组在巴恩斯迷宫和主动位置回避任务中的表现受损。这些行为表现缺陷与海马Iba-1水平升高密切相关，这表明小胶质细胞/巨噬细胞被激活。这些数据表明，CVS→CHI组中更严重的认知缺陷是由于炎症增加所致。CVS→CHI组中缺陷和神经炎症的增加表明，个体经历TBI和PTSD的顺序是TBI/PTSD共病中脑损伤结果的主要决定因素。
