The effect of Na(+)/H(+) exchanger-1 inhibition by sabiporide on blood-brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro.

Abstract

In the present study, we investigated the effects of sabiporide, a specific NHE-1 inhibitor, on blood-brain barrier (BBB) endothelial dysfunction during ischemia/hypoxia in rat cerebral ischemia in vivo and bEnd.3 cells in vitro. Sabiporide significantly attenuated ischemia/hypoxia-induced BBB hyperpermeability and disruption of occludin and zonula occludens-1 both in vivo and in vitro. Sabiporide also inhibited the hypoxia-induced increase in [Ca(2+)](i) in bEnd.3 cells. Taken together, the protective effect of sabiporide on BBB permeability may be mediated through maintaining tight junction integrity and associated with its inhibitory effect on [Ca(2+)](i) overload under hypoxia. These results suggest that the BBB protective effect of sabiporide may be of therapeutical benefit in brain injury after an ischemic stroke.

• Authors: Sung Lyea Park, Dong Ha Lee, Sung-eun Yoo, Yi-Sook Jung
• Journal: Brain research (Brain Res) Vol. 1366 Pg. 189-96 (Dec 17 2010) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 20883671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Carbon Isotopes
• Cytoskeletal Proteins
• Enzyme Inhibitors
• Guanidines
• Membrane Proteins
• Occludin
• Ocln protein, mouse
• Ocln protein, rat
• RNA, Messenger
• Sodium-Hydrogen Exchangers
• growth factor-activatable Na-H exchanger NHE-1
• Evans Blue
• Sucrose
• Calcium
• sabiporide

Topics

• Analysis of Variance
• Animals
• Blood-Brain Barrier (drug effects, physiopathology)
• Brain (cytology)
• Calcium (metabolism)
• Carbon Isotopes (metabolism)
• Cells, Cultured
• Cytoskeletal Proteins (genetics, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (therapeutic use)
• Evans Blue
• Gene Expression (drug effects)
• Guanidines (therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy, pathology, physiopathology)
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• Neuroglia (drug effects, physiology)
• Occludin
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, genetics, metabolism)
• Sucrose (metabolism)
• Tight Junctions (genetics, metabolism)