Preliminary investigation of acute recovery and the influence of anesthetics following blast induced traumatic brain injury in C57BL/6 mice

Abstract

Recognition of traumatic brain injury (TBI) has increased due to higher rates of injuries reported in sports and veterans. Several animal models exist to study TBI, but one that is particularly relevant in recapitulating combat trauma is blast-induced TBI (bTBI). Ethical considerations have resulted in the use of anesthetics and analgesics in virtually all animal models of TBI. However, emerging evidence indicates that anesthetics may provide neuroprotection that could confound results. Therefore, I am determining the level of anesthetic induced neuroprotection in acute recovery (48 Hours) following bTBI by assessing damage sustained to the dentate gyrus, retrosplenial and visual cortices. Using a Cranium Only Blast Injury Apparatus, I delivered non-lethal blast overpressures averaging 534 kiloPascals (kPa) to five groups of adult C57BL/6 mice (control, no anesthetic, xylazine only (13 mg/kg, IP), xylazine/buprenorphine (13 mg/kg, IP and 0.1 mg/kg, SC), and ketamine, xylazine, buprenex (75 mg/kg, IP, 13 mg/kg, IP 0.1 mg/kg, SC). Following recovery, immunocytochemistry was used to visualize changes in: doublecortin (a marker for neurogenesis), parvalbumin and calretinin (two calcium-binding proteins), and the astrocytic marker glial fibrillary acidic protein. My preliminary results show increases in neurogenesis and differential effects of calretinin and parvalbumin in all brain regions following blast injury in the absence of anesthetic and that the use of anesthetics alters these results. Because injuries sustained in combat may not receive medical attention until 48 hours after trauma, this time point can offer valuable information regarding the specific pathways affected and the therapeutic window required for pharmacological intervention.