Cerebral edema is a major contributor to mortality in diverse pathologies; regretfully, no effective therapies can reduce the associated damage. In cerebral ischemia, ionic edema formation is mediated by the sulfonylurea receptor 1 (SUR1)/transient receptor potential melastatin 4 (TRPM4) complex expressed in brain endothelial cells. Given that Resveratrol reduces the damage induced in human brain endothelial cells (HBEC-5i) subjected to oxygen-glucose deprivation (OGD)/reoxiygenation (R) by down-regulating SUR1 expression, we aimed to determine whether Resveratrol modulates SUR1-TRPM4 activity in this model.