Effects of normobaric oxygen and melatonin on reperfusion injury: Role of cerebral microcirculation

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dc.authorid0000-0002-9476-8488
dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-5072-132X
dc.authorid0000-0003-3616-1204
dc.authorid0000-0002-1064-7989
dc.authorid0000-0002-9704-6173
dc.authorid0000-0002-6895-8560
dc.authorid0000-0001-6494-8923
dc.contributor.authorBeker, Mustafa
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorÇa?layan, Berrak
dc.contributor.authorYalçın, Esra
dc.contributor.authorYulu?, Burak
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorHermann, Dirk Matthias
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:02:14Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:02:14Z
dc.date.issued2015
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Nöroloji Ana Bilim Dalı
dc.descriptionWOS: 000363185200028
dc.descriptionPubMed ID: 26416428
dc.description.abstractIn order to protect the brain before an irreversible injury occurs, penumbral oxygenation is the primary goal of current acute ischemic stroke treatment. However, hyperoxia treatment remains controversial due to the risk of free radical generation and vasoconstriction. Melatonin is a highly potent free radical scavenger that protects against ischemic stroke. Considering its anti-oxidant activity, we hypothesized that melatonin may augment the survival-promoting action of normobaric oxygen (NBO) and prevent brain infarction. Herein, we exposed mice to 30 or 90 min of intraluminal middle cerebral artery occlusion (MCAo) and evaluated the effects of NBO (70% or 100% over 90 min), administered either alone or in combination with melatonin (4 mg/ kg, i.p.), on disseminate neuronal injury, neurological deficits, infarct volume, blood-brain barrier (BBB) permeability, cerebral blood flow (CBF) and cell signaling. Both NBO and particularly melatonin alone reduced neuronal injury, neurological deficits, infarct volume and BBB permeability, and increased post-ischemic CBF, evaluated by laser speckle imaging (LSI). They also improved CBF significantly in the ischemic-core and penumbra, which was associated with reduced IgG extravasation, DNA fragmentation, infarct volume, brain swelling and neurological scores. Levels of phosphorylated Akt, anti-apoptotic Bcl-xL, pro-apoptotic Bax and endothelial nitric oxide synthase (NOS) were re-regulated after combined oxygen and melatonin delivery, whereas neuronal and inducible NOS, which were increased by oxygen treatment, were not influenced by melatonin. Our present data suggest that melatonin and NBO are promising approaches for the treatment of acute-ischemic stroke, which encourage proof-of-concept studies in human stroke patients.
dc.description.sponsorshipTUBITAK (The Scientific and Technological Research Council of Turkey) [111S418, 114S402]; Turkish Academy of Sciences (TUBA); EMBO (European Molecular Biology Organization) installation granten_US
dc.description.sponsorshipThis work was supported by TUBITAK (The Scientific and Technological Research Council of Turkey/111S418; 114S402), Turkish Academy of Sciences (TUBA) and EMBO (European Molecular Biology Organization) installation grant.en_US
dc.identifier.citationBeker, M., Çağlayan, A. B., Keleştemur, T., Ça?layan, B., Yalçın, E., Yulu?, B. ... Kılıç, E. (2015). Effects of normobaric oxygen and melatonin on reperfusion injury: Role of cerebral microcirculation. Oncotarget, 6(31), 30604-30614. https://dx.doi.org/10.18632/oncotarget.5773
dc.identifier.doi10.18632/oncotarget.5773
dc.identifier.endpage30614
dc.identifier.issn1949-2553
dc.identifier.issue31
dc.identifier.scopusqualityQ1
dc.identifier.startpage30604
dc.identifier.urihttps://dx.doi.org/10.18632/oncotarget.5773
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3591
dc.identifier.volume6
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherImpact Journals
dc.relation.ispartofOncotargeten_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 3.0 Unported*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/*
dc.subjectHyperoxia
dc.subjectReperfusion Injury
dc.subjectCerebral Microcirculation
dc.subjectBBB Permeability
dc.subjectNOS
dc.subjectPathology Section
dc.titleEffects of normobaric oxygen and melatonin on reperfusion injury: Role of cerebral microcirculation
dc.typeArticle

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