Apoptosis and Necrosis in the Ischemic Zone Adjacent to Third Degree Burns

Abstract

Objectives: Burns are characterized by a central zone of necrosis surrounded by a zone of potentially reversible ischemia. The authors explored the contribution of necrosis and apoptosis to cell death in the zone of ischemia.Methods: A previously established rat contact thermal injury model that utilizes a brass comb to produce four distinctive burns sites separated by three ''interspaces'' of unburned skin was used. The interspaces represent the zone of stasis or ischemia while the burn sites represent the zone of coagulation. With this model, most unburned interspaces progress to necrosis over 2 to 3 days. Full-thickness 3-mm biopsies were obtained from the interspaces, burns, and normal skin controls at 30 minutes, 24 hours, and 48 hours after injury. Slides were stained with hematoxylin and eosin as well as activated cleaved caspase-3 (CC3a) for evidence of apoptosis and high-mobility group box 1 (HMGB1) for evidence of necrosis.Results: Necrosis was not seen at 30 minutes, but was found in a large number of cells within the epidermis, sebaceous glands, and follicles at 24 and 48 hours. Faint nuclear CC3a staining indicative of apoptosis was present in a minority of cells within the epidermis, dermal fibroblasts, dermal follicles, and dermal sebaceous glands at 30 minutes and to a lesser degree at 24 and 48 hours.Conclusions: Both early apoptosis and delayed necrosis are present in the zone of ischemia, contributing to injury progression. Necrosis appears to play a larger role than apoptosis in injury progression in the comb burn model. ACADEMIC EMERGENCY MEDICINE 2008; 15:549-554 ª

Apoptosis is Differentially Regulated by Burn Severity and Dermal Location

“…Other work by Gravante et al using similar methods in humans detected apoptosis in the dermis and cutaneous adnexa, a finding that our study confirms [21]. Our current study also confirms work done on a rat model of third-degree burn that showed apoptotic nuclei by caspase-3 stain early in burn injury (30 min postburn) [15]. Similar to our study, staining was observed in basal keratinocytes of the epidermis, dermal fibroblasts, follicles, and sebaceous glands, and the staining extent decreased at 24 and 48 h post-burn.…”

“…Each slide was allowed to dry at room temperature and then baked at 60 C overnight. Apoptotic or injured/necrotic cells were then identified using proven methods [11,15,21].…”

“…It is presently unclear if burn pathogenesis is mediated by necrosis due to hypoperfusion and ischemia in the burned tissue and the zone of stasis surrounding the injury, or if it is mediated by apoptosis [13][14][15]. The mechanism of cell death in burn depth progression is important because cellular death by necrosis is associated with a much greater inflammatory response than cellular death by apoptosis.…”

A Review of the Local Pathophysiologic Bases of Burn Wound Progression

“…In their study, they used a rat comb thermal injury model. 24 Biopsies were taken from the interspaces of comb-induced full-thickness burns at 30 minutes, 24 hours, and 48 hours postthermal injury. Apoptotic cells were identified by the presence of cleaved caspase-3 (CC3a), and "necrotic" (oncotic) cells were identified by the redistribution of high-mobility group box-1 from the nucleus to the cytoplasm.…”

Role of Autophagy and Apoptosis in Wound Tissue of Deep Second‐degree Burn in Rats

“…Studies have shown that apoptosis and necrosis are both involved in burn wound progression,4 and it has been demonstrated5 that apoptosis is one of the contributing factors of burn wound progression. Inhibiting apoptosis reduces continuous tissue loss and promotes burn wound healing 6.…”