Abstract P193: Estrogen Treatment Following Burn Injury Reduces Brain Inflammation and Apoptotic Signaling
Objective: The objective of this study was to elucidate the effects of acute, post-injury estrogen treatment on IL-1beta, IL-6, IL-10 and TNF-alpha production in the brain following burn injury. Additionally, we wanted to determine the levels of phospho-ERK, phospho-Akt, and caspase 3 in both the placebo and estrogen treated groups, since these pathways are involved in the regulation of inflammation and apoptosis.
Methods: In this study, male rats received a 40% 3rd degree total body surface area (TBSA) burns to the back and flanks, then were fluid resuscitated using the Parkland Burn Formula. Fifteen minutes following the burn injury, the animals received a subcutaneous injection of either placebo or 17 beta-estradiol (0.5 mg/kg). The brains were harvested at 24 hours. We measured brain cytokine levels using the ELISA method, and using Western analysis, we assessed the levels of phosphorylated ERK, phosphorylated Akt, and cleaved caspase 3.
Results: Following burn injury, we found that administration of 17 beta-estradiol significantly (p<0.05) decreased brain levels of IL-1beta (~50%), 1L-6 (~40%), IL-10 (~30%) and TNF-alpha (~25%), compared to those receiving placebo. In addition, we determined that 24 hours post-burn there was an increase in the levels of phospho-ERK and Akt. At this same 24 hour time point, estrogen blocked the cleavage of caspase 3.
Conclusion: Following severe burn injury, estrogen decreases local inflammation and may decrease the activation of apoptosis in the brain, which is supported by our observation of an increase in the levels of phospho-ERK and Akt and inhibition of caspase 3 activation. Results from these studies will help further our understanding of how estrogens protect the brain following burn injury, which in the future may lead to a clinically significant treatment to combat secondary injury and preserve cognition following burn injury.