Anxiety-like Characteristics, Forepaw Thermal Sensitivity Changes and Glial Alterations 1 Month After Repetitive Blast Traumatic Brain Injury in Male Rats

Abstract

Background Many military service members are victims of repetitive blast traumatic brain injuries (rbTBI) and endure diverse altered psychological and behavioural conditions during their lifetime. Some of these conditions include anxiety, post-traumatic stress and pain. Thus, this study attempts to fill the knowledge gap on enduring behavioural and neuroinflammatory marker alterations 1 month after rbTBI. Purpose Although previous rbTBI animal studies have shown behavioural and histopathological changes either a few days (acute) or many months (chronic) after trauma, knowledge related to post-traumatic changes during the intermediate timeframe, i.e. a month after rbTBI is less clear or unavailable. Methods Sprague–Dawley rats (male; n = 12) were assigned to either rbTBI or sham conditions. Animals assigned to the rbTBI group were subjected to 1 blast exposure per day for three consecutive days, while animals in the sham group were exposed to identical experimental conditions sans blast exposure. All animals were tested for anxiety at baseline. 30 days post-injury, animals were tested again for anxiety and paw thermal sensitivity, followed by brain harvest for immunohistochemical analyses. Results Animals exposed to rbTBI showed signs of anxiety-like behaviour on parameters of elevated plus-maze and behavioural signs of pain indicated by reduced thermal withdrawal latency of the forepaw. Histologically, brain sections from animals exposed to rbTBI showed a significantly increased number of microglial/macrophage and astrocytic counts in the medial prefrontal cortex. Conclusion Data from this initial preclinical study support the prevalence of putative anxiety-like behaviour, enhancement in forepaw thermal sensitivity and increase in the number of glial cells even 1 month after rbTBI. These findings have potential implications in the treatment evaluation of blast-exposed military and civilian populations and emphasise the need for devising protective measures for people susceptible to single or repeated exposures. A greater further understanding of rbTBI-related chronic concurrent behavioural and neuropathological sequela is warranted.