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.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Blood-Brain Barrier / drug effects*
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Blood-Brain Barrier / physiopathology
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Brain / cytology
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Calcium / metabolism
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Carbon Isotopes / metabolism
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Cells, Cultured
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / therapeutic use*
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Evans Blue
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Gene Expression / drug effects
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Guanidines / therapeutic use*
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Infarction, Middle Cerebral Artery / drug therapy*
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Infarction, Middle Cerebral Artery / pathology*
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Infarction, Middle Cerebral Artery / physiopathology
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Neuroglia / drug effects
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Neuroglia / physiology
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Occludin
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Sodium-Hydrogen Exchangers / antagonists & inhibitors*
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Sodium-Hydrogen Exchangers / genetics
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Sodium-Hydrogen Exchangers / metabolism
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Sucrose / metabolism
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Tight Junctions / genetics
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Tight Junctions / metabolism
Substances
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Carbon Isotopes
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Cytoskeletal Proteins
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Enzyme Inhibitors
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Guanidines
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Membrane Proteins
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Occludin
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Ocln protein, mouse
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Ocln protein, rat
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RNA, Messenger
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Sodium-Hydrogen Exchangers
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growth factor-activatable Na-H exchanger NHE-1
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Evans Blue
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Sucrose
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Calcium
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sabiporide