Open AccessStatus Epilepticus Induces Vasogenic Edema via Tumor Necrosis Factor-α/ Endothelin-1-Mediated Two Different Pathways
Author(s) -
Jieun Kim,
Hea Jin Ryu,
TaeCheon Kang
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0074458
Subject(s) - status epilepticus , enos , endothelin 1 , tumor necrosis factor alpha , endothelin receptor , astrocyte , nitric oxide , medicine , nadph oxidase , receptor , blood–brain barrier , pulmonary edema , chemistry , endocrinology , pathology , nitric oxide synthase , epilepsy , oxidative stress , central nervous system , lung , psychiatry
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.