Neuroprotective effect of aquaporin-4 deficiency in a mouse model of severe global cerebral ischemia produced by transient 4-vessel occlusion

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dc.contributor.authorAkdemir, Gökhan
dc.contributor.authorRatelade, Julien
dc.contributor.authorAsavapanumas, Nithi
dc.contributor.authorVerkman, A. S.
dc.date.accessioned2020-03-26T18:51:42Z
dc.date.available2020-03-26T18:51:42Z
dc.date.issued2014
dc.departmentSelçuk Üniversitesien_US
dc.description.abstractAstrocyte water channel aquaporin-4 (AQP4) facilitates water movement across the blood-brain barrier and into injured astrocytes. We previously showed reduced cytotoxic brain edema with improved neurological outcome in AQP4 knockout mice in water intoxication, infection and cerebral ischemia. Here, we established a 4-vessel transient occlusion model to test the hypothesis that AQP4 deficiency in mice could improve neurological outcome following severe global cerebral ischemia as occurs in cardiac arrest/resuscitation. Mice were subjected to 10-min transient bilateral carotid artery occlusion at 24h after bilateral vertebral artery cauterization. Cerebral blood flow was reduced during occlusion by >94% in both AQP4(+/+) and AQP4(-/-) mice. The primary outcome, neurological score, was remarkably better at 3 and 5 days after occlusion in AQP4(-/-) than in AQP4(+/+) mice, and survival was significantly improved as well. Brain water content was increased by 2.8 +/- 0.4% in occluded AQP4(+/+) mice, significantly greater than that of 0.3 +/- 0.6% in AQP4(-/-) mice. Histological examination and immunofluorescence of hippocampal sections at 5 days showed significantly greater neuronal loss in the CA1 region of hippocampus in AQP4(+/+) than AQP4(-/-) mice. The neuroprotection in mice conferred by AQP4 deletion following severe global cerebral ischemia provides proof-of-concept for therapeutic AQP4 inhibition to improve neurological outcome in cardiac arrest. (C) 2014 Elsevier Ireland Ltd. All rights reserved.en_US
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK35124, EY13574, EB00415, DK72517]; Guthy-Jackson Charitable Foundationen_US
dc.description.sponsorshipThis work was supported by grants DK35124, EY13574, EB00415 and DK72517 from the National Institutes of Health and grants from the Guthy-Jackson Charitable Foundation.en_US
dc.identifier.doi10.1016/j.neulet.2014.03.073en_US
dc.identifier.endpage75en_US
dc.identifier.issn0304-3940en_US
dc.identifier.issn1872-7972en_US
dc.identifier.pmid24717641en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage70en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.neulet.2014.03.073
dc.identifier.urihttps://hdl.handle.net/20.500.12395/31015
dc.identifier.volume574en_US
dc.identifier.wosWOS:000338616000014en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherELSEVIER IRELAND LTDen_US
dc.relation.ispartofNEUROSCIENCE LETTERSen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectAQP4en_US
dc.subjectNeuroprotectionen_US
dc.subjectWater transporten_US
dc.subjectAstrocyteen_US
dc.subjectBrain edemaen_US
dc.subjectCerebral ischemiaen_US
dc.titleNeuroprotective effect of aquaporin-4 deficiency in a mouse model of severe global cerebral ischemia produced by transient 4-vessel occlusionen_US
dc.typeArticleen_US

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