title: 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.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.
authors.forename: Sung Lyea
authors.initials: SL
authors.lastname: Park
authors.forename: Dong Ha
authors.initials: DH
authors.lastname: Lee
authors.forename: Sung-eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Yi-Sook
authors.initials: YS
authors.lastname: Jung
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001921:Brain / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002247:Carbon Isotopes / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005070:Evans Blue; D015870:Gene Expression / Q000187:drug effects; D006146:Guanidines / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D062793:Occludin; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D006146:Guanidines; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; C568987:Ocln protein, rat; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D005070:Evans Blue; D013395:Sucrose; D002118:Calcium; C476560:sabiporide