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Article: Normobaric hyperoxia attenuates early blood-brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemia

TitleNormobaric hyperoxia attenuates early blood-brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemia
Authors
Issue Date2009
Citation
Journal Of Neurochemistry, 2009, v. 108 n. 3, p. 811-820 How to Cite?
AbstractEarly blood-brain barrier (BBB) disruption resulting from excessive neurovascular proteolysis by matrix metalloproteinases (MMPs) is closely associated with hemorrhagic transformation events in ischemic stroke. We have shown that normobaric hyperoxia (NBO) treatment reduces MMP-9 increase in the ischemic brain. The aim of this study was to determine whether NBO could attenuate MMP-9-mediated early BBB disruption following ischemic stroke. Rats were exposed to NBO (95% O2) or normoxia (30% O2) during 90-min middle cerebral artery occlusion, followed by 3-hour reperfusion. NBO-treated rats showed a significant reduction in Evan's blue extravasation in the ischemic hemisphere compared with normoxic rats. Topographically, Evan's blue leakage was mainly seen in the subcortical regions including the striatum, which was accompanied by increased gelatinolytic activity and reduced immunostaining for tight-junction protein, occludin. Increased gelatinolytic activities and occludin protein loss were also observed in isolated ischemic microvessels. Gel gelatin zymography identified that MMP-9 was the main enzymatic source in the cerebral microvessels. Incubation of brain slices or isolated microvessels with purified MMP-9 revealed specific degradation of occludin. Inhibition of MMP-9 by NBO or MMP-inhibitor, BB1101, significantly reduced occludin protein loss in ischemic microvessels. These results suggest that NBO attenuates early BBB disruption, and inhibition of MMP-9-mediated occludin degradation is an important mechanism for this protection. © 2008 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/179450
ISSN
2015 Impact Factor: 3.842
2015 SCImago Journal Rankings: 2.021
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Wen_US
dc.contributor.authorHendren, Jen_US
dc.contributor.authorQin, XJen_US
dc.contributor.authorShen, Jen_US
dc.contributor.authorLiu, KJen_US
dc.date.accessioned2012-12-19T09:56:41Z-
dc.date.available2012-12-19T09:56:41Z-
dc.date.issued2009en_US
dc.identifier.citationJournal Of Neurochemistry, 2009, v. 108 n. 3, p. 811-820en_US
dc.identifier.issn0022-3042en_US
dc.identifier.urihttp://hdl.handle.net/10722/179450-
dc.description.abstractEarly blood-brain barrier (BBB) disruption resulting from excessive neurovascular proteolysis by matrix metalloproteinases (MMPs) is closely associated with hemorrhagic transformation events in ischemic stroke. We have shown that normobaric hyperoxia (NBO) treatment reduces MMP-9 increase in the ischemic brain. The aim of this study was to determine whether NBO could attenuate MMP-9-mediated early BBB disruption following ischemic stroke. Rats were exposed to NBO (95% O2) or normoxia (30% O2) during 90-min middle cerebral artery occlusion, followed by 3-hour reperfusion. NBO-treated rats showed a significant reduction in Evan's blue extravasation in the ischemic hemisphere compared with normoxic rats. Topographically, Evan's blue leakage was mainly seen in the subcortical regions including the striatum, which was accompanied by increased gelatinolytic activity and reduced immunostaining for tight-junction protein, occludin. Increased gelatinolytic activities and occludin protein loss were also observed in isolated ischemic microvessels. Gel gelatin zymography identified that MMP-9 was the main enzymatic source in the cerebral microvessels. Incubation of brain slices or isolated microvessels with purified MMP-9 revealed specific degradation of occludin. Inhibition of MMP-9 by NBO or MMP-inhibitor, BB1101, significantly reduced occludin protein loss in ischemic microvessels. These results suggest that NBO attenuates early BBB disruption, and inhibition of MMP-9-mediated occludin degradation is an important mechanism for this protection. © 2008 The Authors.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Neurochemistryen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlood-Brain Barrier - Drug Effectsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCapillaries - Drug Effects - Physiologyen_US
dc.subject.meshColoring Agentsen_US
dc.subject.meshEvans Blueen_US
dc.subject.meshGelatin - Metabolismen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshInfarction, Middle Cerebral Artery - Metabolism - Pathologyen_US
dc.subject.meshIschemic Attack, Transient - Metabolism - Pathologyen_US
dc.subject.meshMatrix Metalloproteinase 2 - Metabolismen_US
dc.subject.meshMatrix Metalloproteinase 9 - Antagonists & Inhibitors - Physiologyen_US
dc.subject.meshMembrane Proteins - Metabolismen_US
dc.subject.meshOxygen Inhalation Therapyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReperfusion Injury - Metabolism - Pathologyen_US
dc.subject.meshTight Junctions - Drug Effectsen_US
dc.titleNormobaric hyperoxia attenuates early blood-brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemiaen_US
dc.typeArticleen_US
dc.identifier.emailShen, J: shenjg@hku.hken_US
dc.identifier.authorityShen, J=rp00487en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1471-4159.2008.05821.xen_US
dc.identifier.pmid19187098-
dc.identifier.scopuseid_2-s2.0-58149326864en_US
dc.identifier.hkuros154246-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58149326864&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume108en_US
dc.identifier.issue3en_US
dc.identifier.spage811en_US
dc.identifier.epage820en_US
dc.identifier.isiWOS:000262348600025-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLiu, W=7407343965en_US
dc.identifier.scopusauthoridHendren, J=15839600100en_US
dc.identifier.scopusauthoridQin, XJ=7202154954en_US
dc.identifier.scopusauthoridShen, J=7404929947en_US
dc.identifier.scopusauthoridLiu, KJ=7404200456en_US
dc.identifier.citeulike3904212-

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