ABSTRACT
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 â CVS) or CVS then CHI (CVS â CHI). The CVS â CHI group had deficits in Barnes maze or active place avoidance not seen in the other groups. The CVS â CHI, CVS and CHI â CVS groups displayed increased basal anxiety level, based on performance on elevated plus maze. The CVS â 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 â CHI group were due to increased inflammation. The increased deficits and neuroinflammation in the CVS â 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.