Co-morbid
mild traumatic brain injury (mTBI) and
post-traumatic stress disorder (
PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and
PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for
PTSD and combined
PTSD-mTBI. The
PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a
physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint.
PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in
PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in
corticosterone in
PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory
cytokine(s) in the
PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated
trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and
ICAM-1 respectively. Our observations thus far suggest that this novel stress-
trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and
PTSD experienced by combat veterans.