Status Epilepticus Induces Vasogenic Edema via Tumor Necrosis Factor-α/ Endothelin-1-Mediated Two Different Pathways

Status epilepticus (SE) induces vasogenic edema in the piriform cortex with disruptions of the blood-brain barrier (BBB). However, the mechanisms of vasogenic edema formation following SE are still unknown. Here we investigated the endothelin B (ET(B)) receptor-mediated pathway of SE-induced vasogenic edema. Following SE, the release of tumor necrosis factor-α (TNF-α) stimulated endothelin-1 (ET-1) release and expression in neurons and endothelial cells. In addition, TNF-α-induced ET-1 increased BBB permeability via ET(B) receptor-mediated endothelial nitric oxide synthase (eNOS) activation in endothelial cells. ET(B) receptor activation also increased intracellular reactive oxygen species by NADPH oxidase production in astrocytes. These findings suggest that SE results in BBB dysfunctions via endothelial-astroglial interactions through the TNF-α-ET-1-eNOS/NADPH oxidase pathway, and that these ET(B) receptor-mediated interactions may be an effective therapeutic strategy for vasogenic edema in various neurological diseases.