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

• Published in: Brain research 2010-12, Vol.1366, p.189-196
• Main Authors: Park, Sung Lyea, Lee, Dong Ha, Yoo, Sung-eun, Jung, Yi-Sook
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiopathology; Blood–brain barrier; Brain - cytology; Calcium - metabolism; Carbon Isotopes - metabolism; Cells, Cultured; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors - therapeutic use; Evans Blue; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Guanidines - therapeutic use; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - physiopathology; Ischemia/hypoxia; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Na +/H + exchanger-1; Neuroglia - drug effects; Neuroglia - physiology; Neurology; Occludin; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Sabiporide; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Sodium-Hydrogen Exchangers - genetics; Sodium-Hydrogen Exchangers - metabolism; Sucrose - metabolism; Tight junction protein; Tight Junctions - genetics; Tight Junctions - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.09.077

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 [Ca2+ ]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 [Ca2+ ]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.