Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with patients often suffering from consequences such as cognitive deficits, social abnormalities, anxiety, depression, pain, and motor dysfunction. Given that these impairments often have a significant impact on the patient's quality of life, a key aim of therapeutic intervention in TBI is to mitigate these effects. Translational strategies to develop such interventions have heavily featured animal models of TBI. To assess the efficacy of interventions in these models, a range of behavioral outcomes are utilized. However, in light of the past translational failures that have plagued the TBI field, the clinical relevance of these preclinical behavioral tests is now being scrutinized. This article will summarize the behavioral consequences of TBI in humans; describe common methods available for testing cognition, social function, motor ability, pain, as well as depression-and anxiety-like behaviors in animal models of TBI; provide an overview of the results from TBI animal model studies that have utilized these methods; and discuss these pre-clinical behavior methods and findings in terms of their relevance to the clinical TBI setting. We conclude that there is translational value in these methods and their related findings, but also suggest strategies and future research to improve the clinical relevance of behavior testing in animal models of TBI.

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours). In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau), in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored.

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