['Patients with severe burn injury experience a rapid elevation in multiple circulating pro-inflammatory cytokines, with the levels correlating with both injury severity and outcome. Accumulations of these cytokines in animal models have been observed in remote organs, however data are lacking regarding early brain cytokine levels following burn injury, and the effects of estradiol on these levels. Using an experimental animal model, we studied the acute effects of a full-thickness third degree burn on brain levels of TNF-alpha, IL-1beta, and IL-6 and the protective effects of acute estrogen treatment on these levels. Additionally, the acute administration of estrogen on regulation of inflammatory and apoptotic events in the brain following severe burn injury were studied through measuring the levels of phospho-ERK, phospho-Akt, active caspase-3, and PARP cleavage in the placebo and estrogen treated groups.', 'In this study, 149 adult Sprague-Dawley male rats received 3rd degree 40% total body surface area (TBSA) burns. Fifteen minutes following burn injury, the animals received a subcutaneous injection of either placebo (n = 72) or 17 beta-estradiol (n = 72). Brains were harvested at 0.5, 1, 2, 4, 6, 8, 12, 18, and 24 hours after injury from the control (n = 5), placebo (n = 8/time point), and estrogen treated animals (n = 8/time point). The brain cytokine levels were measured using the ELISA method. In addition, we assessed the levels of phosphorylated-ERK, phosphorylated-Akt, active caspase-3, and the levels of cleaved PARP at the 24 hour time-point using Western blot analysis.', 'In burned rats, 17 beta-estradiol significantly decreased the levels of brain tissue TNF-alpha (approximately 25%), IL-1beta (approximately 60%), and IL-6 (approximately 90%) when compared to the placebo group. In addition, we determined that in the estrogen-treated rats there was an increase in the levels of phospho-ERK (p < 0.01) and Akt (p < 0.05) at the 24 hour time-point, and that 17 beta-estradiol blocked the activation of caspase-3 (p < 0.01) and subsequent cleavage of PARP (p < 0.05).'] Do estrogen treatment following severe burn injury reduces brain inflammation and apoptotic signaling?