Dexamethasone restores blood–brain barrier integrity in an in vitro heatstroke model

Abstract

Heat-related diseases and their treatments are becoming the center of focus due to global warming resulting in rising global temperatures. Heatstroke is the most hazardous condition of heat-related diseases, which when left untreated leads to death. One of the main characteristics of heatstroke is the dysfunction of the central nervous system. In this study, we established an in vitro heatstroke model of the blood–brain barrier (BBB) consisting of endothelial cells and pericytes. Following heat exposure at 43°C for 3 h, the model failed to recover during the subsequent 24 h regeneration period. The damage was shown by decreased transendothelial resistance (p < 0,0001) and confirmed by permeability assays and immunohistochemistry with in silico analysis. We subsequently evaluated the effect of dexamethasone in our heatstroke model. Administration of dexamethasone post-heatstroke alleviated BBB damage during the regeneration period, by increasing transendothelial electrical resistance and ZO-1 expression while reducing BBB permeability. Our findings suggest that dexamethasone reduces heatstroke damage at the BBB in in vitro conditions.