Post stress treatment of burn injuries

Extensive heat has devastating effects on living cells. During burn injuries immediate lysis occurs in the regions with the highest temperatures. The cells in the adjacent zone of stasis potentially survive, but are severely affected by the heat. In addition, their environment in the tissue changes due to hypoperfusion and edema. Together with infections these conditions can dramatically impair the survival of the cells and finally lead to complete necrosis in this tissue zone. This phenomenon is known as burn wound progression, which represents a major complication for the treatment. Furthermore deep burn wounds substantially compromise the quality of life for the patients after recovery. Equally important to the reactions of the tissue is a consideration of the damages at the cellular level. The most critical result of the heat exposure are denatured proteins, which block the cellular pathways and therefore represent a major burden. If not eliminated, they dramatically reduce the survival rate, particularly during subsequent conditions of burn wound progression. The removal of denatured proteins is accomplished by the heat shock response, a pathway conserved from bacteria to humans. We analyzed this cellular pathway and found a slow response after short heat exposure at high temperatures. We therefore hypothesized an improvement of cell survival by a special "post stress treatment" (PST). The rationale of this method is to accelerate the heat shock response by a moderate stress treatment after the heat pulse. Although the PST in these preliminary experiments substantially increased the total stress for the cells, we indeed could demonstrate a clear improvement in survival. In this project we will systematically examine the heat shock pathway regulation after short heat treatment. These experiments will be performed in cell culture cells and in fish embryos, which allow a genetic dissection of the pathway. As a result, we will obtain critical markers of the pathway, which we can use in the subsequent experiments. Main goal of the project is the optimization of a PST for burn injuries. Prime candidates for the PST are pharmacologic modulators of the heat shock response, which can activate the pathway without imposing additional stress.

No additional funding sources recorded.