Exposure to Acute Psychological Trauma Prior to Blast Neurotrauma Results in Alternative Behavioral Outcomes

Stress is a common occurrence for military personnel. This can include the stress of deployment and active combat. Anxiety is considered a reaction to stress and with anxiety related disorders on the rise, it is imperative that stress be considered a pre-existing condition when studying a number of neurological conditions. To determine the effects of stress on the behavioral outcomes of traumatic brain injury (TBI), we used a 3-day acute unpredictable stress (AUS) model followed by blast induce neurotrauma (BINT) to assessed social anhedonia and anxiety-like behaviors in male and female rats. The animals were divided into 4 groups including an unstressed and uninjured control (Con), stress only animals (AUS), injury only animals (BINT), and animals that received both stress and injury (AUS+BINT). In the males, behavioral tests such as elevated plus and 3-chamber sociability showed that stress plays a dominant role in determining behavioral outcomes after TBI with the AUS+BINT animals behaving more similarly to the AUS animals than the BINT animals. Other tests, such as open field, showed that AUS+BINT had an additive effect on anxiety-like behavior or that pre stress could even have a protective effect as seen in 3-chamber social novelty. Behavioral assessment of female animals showed that AUS+BINT had the opposite effect than it did on the males in both 3-chamber sociability and 3-chamber social novelty, while the open field results were similar to the males. This study shows that neurological changes driven by stress have an effect on the behavioral outcomes of BINT.<b>Significance Statement</b> It has been well established that exposure to even acutely stressful situations can cause long lasting neurological and behavioral changes. While many studies have focused on the neuropathological and psychological aspects of TBI and stress separately, the relationship between the two is understudied. Current preclinical models of TBI actively attempt to minimize the animal's exposure to stress to prevent any stress-induced neurological changes from interfering with TBI-related outcomes. Here we demonstrate that, by not factoring in stress-induced neurological changes, we are limiting the clinical relevancy of the TBI model given that stress is an everyday factor in human populations.