The effect of Na(+)/H(+) exchanger-1 inhibition by sabiporide on blood-brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro.
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.
Park
Sung Lyea
SL
Department of Physiology, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.
Lee
Dong Ha
DH
Yoo
Sung-eun
SE
Jung
Yi-Sook
YS
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
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