Chronological changes in rat heel skin following depressurization of pressure ulcer-like dermal lesions

Abstract

In our previous study, we proposed an animal model in which pressure ulcer-like dermal lesions can be produced by denervation of the sciatic nerve and application of a pressure load to rat heel skin. In the present study, we divided these animals into non-treated and pressure loading groups, and initiated hindlimb unloading (depressurization) by tail suspension at 1, 3, 5, 7, and 14 days after inflicting lesions (1–14d pressurization groups). Chronological changes in heel lesions were examined morphologically in all treatment groups after 1, 3, 7, 14, 28, and 40 days. Open dermal lesions were formed by 14 days in the loading group and numerous macrophages were present. In the 14d pressurization group, numerous macrophages were still distributed in and around lesions and Vascular endothelial cell growth factor (VEGF) expression was strongly detected by 3 days, but a thin germinal layer began to appear and CD68-positive macrophages and VEGF immunoreactions decreased gradually by 7 days later. By 14 days after depressurization, the germinal layer was repaired, and macrophages and immunoreactions of VEGF were similar to those of non-treated skin. These chronological changes were similar to those in human pressure ulcers, but from 5d after depressurization, different chronological changes were observed. Specifically, epidermis was thickened and macrophages were hardly detected at 5 days in the loading group, but the epidermis disappeared by 1 day in the 5d pressurization group. Subsequently, numerous macrophages aggregated and VEGF expression was increased by 3 days, and the remaining healing process was similar to that in the 14d pressurization group. Even when unloading was performed during the early stages (5d pressurization group), the epidermis disappeared and macrophages were then distributed before repair of the lesion was observed. These results suggest that earlier migration of macrophages to skin lesions might be associated with rapid wound healing.