Spatiotemporal progression of cell death in the zone of ischemia surrounding burns

Abstract

Burns are dynamic injuries, characterized by progressive death of surrounding tissue over time. Although central to an understanding of burn injury progression, the spatiotemporal degrees and rates of cellular necrosis and apoptosis in the zone of ischemia surrounding burns are not well characterized. Using a validated porcine hot comb model, we probed periburn tissue at 1, 4, and 24 hours after injury for high-mobility group box 1 as a marker of necrosis and activated cleaved caspase-3 as a marker of apoptosis, followed by spatiotemporal morphometric analysis. We found that necrosis was the most prominent mechanism of cell death in burn injury progression, with significant progression between 1 and 4 hours postburn. Apoptosis appeared not to play a role in early burn injury progression but was observed in cells at the interface of necrotic and viable tissue at 24 hours postburn. Our findings imply that intervention within the first 4 hours following injury is likely necessary to limit burn injury progression. Additionally, based on high-mobility group box 1 staining patterns, we define distinct early, intermediate, and late pathological signs of cell necrosis that may facilitate delineation of causal mechanistic relationships of burn injury progression in vivo.