title: Activation of estrogen receptor β reduces blood-brain barrier breakdown following ischemic injury.
abstract: Estrogen receptors (ERs) play important roles in estrogen-mediated neuroprotection. However, their effects on blood-brain barrier (BBB) disruption with vasogenic edema after ischemic stroke have not been determined. We evaluated a role for ERβ in the brain without effects in the peripheral reproductive organs for the amelioration of vasogenic edema following ischemic stroke. Transient focal ischemic stroke was induced in ovariectomized female C57BL/6 mice (age 10-11weeks) that were treated with the ERβ-selective agonist diarylpropionitrile (DPN). BBB breakdown as determined by the extravasation of endogenous immunoglobulin G (IgG), vasogenic edema, and the infarct volume was significantly reduced by DPN compared to vehicle. Protein expressions of endothelial tight junction proteins (occludin and claudin-5) and the water channel protein aquaporin 4 in the ischemic cortex were not changed by DPN. However, protein levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α), a transcription factor that increases VEGF expression, were significantly decreased in the ischemic cortex by DPN. These results suggest that ERβ contributes to the reduction of vasogenic edema caused by BBB breakdown via the inhibition of HIF-1α and VEGF following ischemic stroke.
authors: Department of Pharmacology, Tissue Injury Defense Research Center, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors: J A
authors: JA
authors: Shin
authors: S J
authors: SJ
authors: Yang
authors: S I
authors: SI
authors: Jeong
authors: H J
authors: HJ
authors: Park
authors: Y-H
authors: YH
authors: Choi
authors: E-M
authors: EM
authors: Park
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000473:pathology*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D062507:Claudin-5 / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists*; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology; D062793:Occludin / Q000378:metabolism; D010052:Ovariectomy; D011422:Propionates / Q000494:pharmacology; D019108:Tight Junctions / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D000199:Actins; D051401:Aquaporin 4; D062507:Claudin-5; D047629:Estrogen Receptor beta; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007074:Immunoglobulin G; D009570:Nitriles; D062793:Occludin; D011422:Propionates; D042461:Vascular Endothelial Growth Factor A