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

Authors
Park, SL; Lee, DH; Yoo, SE; Jung, YS
Citation
Brain research, 1366189-196, 2010
Journal Title
Brain research
ISSN
0006-89931872-6240
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.
MeSH terms
Analysis of VarianceAnimalsBlood-Brain Barrier/drug effects*Blood-Brain Barrier/physiopathologyBrain/cytologyCalcium/metabolismCarbon Isotopes/metabolismCells, CulturedCytoskeletal Proteins/geneticsCytoskeletal Proteins/metabolismDisease Models, AnimalDose-Response Relationship, DrugEnzyme Inhibitors/therapeutic use*Evans Blue/diagnostic useGene Expression/drug effectsGuanidines/therapeutic use*Infarction, Middle Cerebral Artery/drug therapy*Infarction, Middle Cerebral Artery/pathology*Infarction, Middle Cerebral Artery/physiopathologyMaleMembrane Proteins/geneticsMembrane Proteins/metabolismMiceNeuroglia/drug effectsNeuroglia/physiologyRNA, Messenger/metabolismRatsRats, Sprague-DawleySodium-Hydrogen Antiporter/antagonists & inhibitors*Sodium-Hydrogen Antiporter/geneticsSodium-Hydrogen Antiporter/metabolismSucrose/metabolismTight Junctions/geneticsTight Junctions/metabolism
DOI
10.1016/j.brainres.2010.09.077
PMID
20883671
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
정, 이숙
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