Sustained neurological recovery induced by resveratrol is associated with angioneurogenesis rather than neuroprotection after focal cerebral ischemia

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dc.authorid0000-0002-6242-3709
dc.authorid0000-0001-6494-8923
dc.contributor.authorHermann, Dirk Matthias
dc.contributor.authorZechariah, Anil
dc.contributor.authorKaltwasser, Britta
dc.contributor.authorBosche, Bert
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorKılıç, Ertuğrul
dc.contributor.authorDoeppner, Thorsten Roland
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:01:56Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:01:56Z
dc.date.issued2015
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.descriptionWOS: 000366230000002
dc.descriptionPubMed ID: 26316359
dc.description.abstractAccording to the French paradox, red wine consumption reduces the incidence of vascular diseases even in the presence of highly saturated fatty acid intake. This phenomenon is widely attributed to the phytoalexin resveratrol, a red wine ingredient. Experimental studies suggesting that resveratrol has neuroprotective properties mostly used prophylactic delivery strategies associated with short observation periods. These studies did not allow conclusions to be made about resveratrol's therapeutic efficacy post-stroke. Herein, we systematically analyzed effects of prophylactic, acute and post-acute delivery of resveratrol (50 mg/kg) on neurological recovery, tissue survival, and angioneurogenesis after focal cerebral ischemia induced by intraluminal middle cerebral artery occlusion in mice. Over an observation period of four weeks, only prolonged post-acute resveratrol delivery induced sustained neurological recovery as assessed by rota rod, tight rope and corner turn tests. Although prophylactic and acute resveratrol delivery reduced infarct volume and enhanced blood-brain-barrier integrity at 2 days post-ischemia by elevating resveratrol's downstream signal sirtuin-1, increasing cell survival signals (phosphorylated Akt, heme oxygenase-1, Bcl-2) and decreasing cell death signals (Bax, activated caspase-3), a sustained reduction of infarct size on day 28 was not observed in any of the three experimental conditions. Instead, enhanced angiogenesis and neurogenesis were noted in animals receiving post-acute resveratrol delivery, which were associated with elevated concentrations of GDNF and VEGF in the brain. Thus, sustained neurological recovery induced by resveratrol depends on successful brain remodeling rather than structural neuroprotection. The recovery promoting effect of delayed resveratrol delivery opens promising perspectives for stroke therapy.
dc.description.sponsorshipTUBITAK [2221]; German Research Council [HE3173/2-2, HE3173/3-1]en_US
dc.description.sponsorshipThis work was supported by TUBITAK (grant #2221 to TRD) and by the German Research Council (grants #HE3173/2-2 and #HE3173/3-1 to DMH).en_US
dc.identifier.citationHermann, D. M., Zechariah, A., Kaltwasser, B., Bosche, B., Çağlayan, A. B., Kılıç, E. ve Doeppner, T. R. (2015). Sustained neurological recovery induced by resveratrol is associated with angioneurogenesis rather than neuroprotection after focal cerebral ischemia. Neurobiology of Disease, 83,16-25. https://dx.doi.org/10.1016/j.nbd.2015.08.018
dc.identifier.doi10.1016/j.nbd.2015.08.018
dc.identifier.endpage25
dc.identifier.issn0969-9961
dc.identifier.issn1095-953X
dc.identifier.scopusqualityQ1
dc.identifier.startpage16
dc.identifier.urihttps://dx.doi.org/10.1016/j.nbd.2015.08.018
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3497
dc.identifier.volume83
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press
dc.relation.ecinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/2221
dc.relation.ispartofNeurobiology of Diseaseen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAngiogenesis
dc.subjectCerebral Ischemia
dc.subjectNeurogenesis
dc.subjectNeuroprotection
dc.subjectNeuroregeneration
dc.subjectStroke
dc.titleSustained neurological recovery induced by resveratrol is associated with angioneurogenesis rather than neuroprotection after focal cerebral ischemia
dc.typeArticle

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