The unconventional growth factors cerebral dopamine neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor promote post-ischemic neurological recovery, perilesional brain remodeling, and lesion-remote axonal plasticity

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dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-9476-8488
dc.authorid0000-0002-5072-132X
dc.authorid0000-0002-6637-9944
dc.authorid0000-0002-2657-3515
dc.authorid0000-0003-2251-2093
dc.authorid0000-0002-1222-9211
dc.authorid0000-0001-6494-8923
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorSertel Evren, Elif
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorAteş, Nilay
dc.contributor.authorÇağlayan, Aysun
dc.contributor.authorDaşdelen, Muhammed Furkan
dc.contributor.authorDoeppner, Thorsten Roland
dc.contributor.authorSaarma, Mart
dc.contributor.authorHermann, Dirk Matthias
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2023-09-13T07:53:28Z
dc.date.available2023-09-13T07:53:28Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı
dc.description.abstractConsiderable efforts are currently made to develop strategies that boost endogenous recovery once a stroke has occurred. Owing to their restorative properties, neurotrophic factors are attractive candidates that capitalize on endogenous response mechanisms. Non-conventional growth factors cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) promote neuronal survival and reduce neurological deficits in the acute phase of ischemic stroke in mice. Their effects on endogenous repair and recovery mechanisms in the stroke recovery phase were so far unknown. By intracerebroventricular delivery of CDNF or MANF starting 3 days post-stroke (1 mu g/day for 28 days via miniosmotic pumps), we show that delayed CDNF and MANF administration promoted functional neurological recovery assessed by a battery of behavioral tests, increased long-term neuronal survival, reduced delayed brain atrophy, glial scar formation, and, in case of CDNF but not MANF, increased endogenous neurogenesis in the perilesional brain tissue. Besides, CDNF and MANF administration increased long-distance outgrowth of terminal axons emanating from the contralesional pyramidal tract, which crossed the midline to innervate ipsilesional facial nucleus. This plasticity promoting effect was accompanied by downregulation of the axonal growth inhibitor versican and the guidance molecules ephrin B1 and B2 in the previously ischemic hemisphere at 14 dpi, which represents a sensitive time-point for axonal growth. CDNF and MANF reduced the expression of the proinflammatory cytokines IL1 beta and TNF alpha in both hemispheres. The effects of non-conventional growth factors in the ischemic brain should further be examined since they might help to identify targets for restorative stroke therapy.
dc.description.sponsorshipTurkish Academy of Sciencesen_US
dc.identifier.citationÇağlayan, A. B., Beker, M. Ç., Sertel Evren, E., Çağlayan, B., Kılıç, Ü., Ateş, N. ... Kılıç, E. (2023). The unconventional growth factors cerebral dopamine neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor promote post-ischemic neurological recovery, perilesional brain remodeling, and lesion-remote axonal plasticity. Translational Stroke Research, 14(2), 263-277. https://dx.doi.org/10.1007/s12975-022-01035-2
dc.identifier.doi10.1007/s12975-022-01035-2
dc.identifier.endpage277
dc.identifier.issn1868-4483
dc.identifier.issn1868-601X
dc.identifier.issue2
dc.identifier.pmid35583716
dc.identifier.scopus2-s2.0-85130262283
dc.identifier.scopusqualityQ1
dc.identifier.startpage263
dc.identifier.urihttps://dx.doi.org/10.1007/s12975-022-01035-2
dc.identifier.urihttps://hdl.handle.net/20.500.12511/11417
dc.identifier.volume14
dc.identifier.wos000797290700001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorÇağlayan, Ahmet Burak
dc.institutionauthorBeker, Mustafa Çağlar
dc.institutionauthorSertel Evren, Elif
dc.institutionauthorÇağlayan, Berrak
dc.institutionauthorAteş, Nilay
dc.institutionauthorÇağlayan, Aysun
dc.institutionauthorDaşdelen, Muhammed Furkan
dc.institutionauthorDoeppner, Thorsten Roland
dc.institutionauthorKılıç, Ertuğrul
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofTranslational Stroke Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/114S402
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAxonal Sprouting
dc.subjectCDNF
dc.subjectFocal Cerebral Ischemia
dc.subjectIschemic Stroke
dc.subjectMANF
dc.subjectUnconventional Growth Factor
dc.titleThe unconventional growth factors cerebral dopamine neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor promote post-ischemic neurological recovery, perilesional brain remodeling, and lesion-remote axonal plasticity
dc.typeArticle

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