Inhibition of Hypoxia-Induced Increase of Blood-Brain Barrier Permeability by YC-1 through the Antagonism of HIF-1α Accumulation and VEGF Expression

• DOI: 10.1124/mol.107.036418
• Publication Date: 2007-05-19T14:27:05Z
• Authors: Wei-Lan Yeh; Dah-Yuu Lu; Chun-Jung Lin; Houng-Chi Liou; Wen-Mei Fu
• Keywords: Hypoxia; Fluorescein isothiocyanate; Vascular permeability; Occludin

Cerebral microvascular endothelial cells form the anatomical basis of blood-brain barrier (BBB), and tight junctions BBB are critical for maintaining brain homeostasis low permeability. Ischemia/reperfusion is known to damage lead permeability changes. Here we investigated protective role 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), against chemical hypoxia hypoxia/reoxygenation (H/R)-induced hyperpermeability using adult rat cell culture (ARBEC). YC-1 significantly decreased CoCl₂- H/R-induced fluorescein isothiocyanate (FITC)-dextran in inserts. It was found that decrease disorganization junction protein zonular occludens-1 (ZO-1) response CoCl₂, H/R antagonized by YC-1. The protection may result from inhibition HIF-1α accumulation production its downstream target vascular growth factor (VEGF). VEGF alone increased FITC-dextran down-regulated mRNA levels ZO-1 ARBECs. We further used animal model examine effect on after cerebral ischemia/reperfusion. protected ischemia/reperfusion-induced injury. Taken together, these results indicate inhibit production, which turn protect injury caused hypoxia.