Lentivirally administered glial cell line-derived neurotrophic factor promotes post-ischemic neurological recovery, brain remodeling and contralesional pyramidal tract plasticity by regulating axonal growth inhibitors and guidance proteins

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dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-9476-8488
dc.authorid0000-0002-4051-2559
dc.authorid0000-0002-9013-2298
dc.authorid0000-0001-6494-8923
dc.contributor.authorBeker, Merve
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorAltunay, Serdar
dc.contributor.authorKaraçay, Reyda
dc.contributor.authorDalay, Arman
dc.contributor.authorAltıntaş, Mehmet Özgen
dc.contributor.authorTorun Köse, Gamze
dc.contributor.authorHermann, Dirk M.
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2020-09-30T07:02:22Z
dc.date.available2020-09-30T07:02:22Z
dc.date.issued2020
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractOwing to its potent longterm neuroprotective and neurorestorative properties, glial cell line-derived neurotrophic factor (GDNF) is currently studied in neurodegenerative disease clinical trials. However, little is known about the longterm effect of GDNF on neurological recovery, brain remodeling and neuroplasticity in the post-acute phase of ischemic stroke. In a comprehensive set of experiments, we examined the effects of lentiviral GDNF administration after ischemic stroke. GDNF reduced neurological deficits, neuronal injury, blood-brain barrier permeability in the acute phase in mice. As compared with control, enhanced motor-coordination and spontaneous locomotor activity were noted in GDNF-treated mice, which were associated with increased microvascular remodeling, increased neurogenesis and reduced glial scar formation in the peri-infarct tissue. We observed reduced brain atrophy and increased plasticity of contralesional pyramidal tract axons that crossed the midline in order to innervate denervated neurons in the ipsilesional red and facial nuclei. Contralesional axonal plasticity by GDNF was associated with decreased abundance of the axonal growth inhibitors brevican and versican in contralesional and ipsilesional brain tissue, reduced abundance of the growth repulsive guidance molecule ephrin b1 in contralesional brain tissue, increased abundance of the midline growth repulsive protein Slit1 in contralesional brain tissue and reduced abundance of Slit1's receptor Robo2 in ipsilesional brain tissue. These data indicate that GDNF potently induces longterm neurological recovery, peri-infarct brain remodeling and contralesional neuroplasticity, which are associated with the fine-tuned regulation of axonal growth inhibitors and guidance molecules that facilitate the growth of contralesional corticofugal axons in the direction to the ipsilesional hemisphere.
dc.description.sponsorshipTurkish Academy of Sciences Bezmialem Vakif Universityen_US
dc.identifier.citationBeker, M., Çağlayan, A. B., Beker, M. Ç., Altunay, S., Karaçay, R., Dalay, A. ... Kılıç, E. (2020). Lentivirally administered glial cell line-derived neurotrophic factor promotes post-ischemic neurological recovery, brain remodeling and contralesional pyramidal tract plasticity by regulating axonal growth inhibitors and guidance proteins. Experimental Neurology, 331. https://dx.doi.org/10.1016/j.expneurol.2020.113364
dc.identifier.doi10.1016/j.expneurol.2020.113364
dc.identifier.issn0014-4886
dc.identifier.issn1090-2430
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.1016/j.expneurol.2020.113364
dc.identifier.urihttps://hdl.handle.net/20.500.12511/5889
dc.identifier.volume331
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofExperimental Neurologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAxonal Plasticity
dc.subjectAnterograde Tract Tracing
dc.subjectFocal Cerebral Ischemia
dc.subjectGrowth Inhibitor
dc.subjectGuidance Cue
dc.subjectMiddle Cerebral Artery Occlusion
dc.subjectMidline Repellent
dc.subjectNeuronal Plasticity
dc.titleLentivirally administered glial cell line-derived neurotrophic factor promotes post-ischemic neurological recovery, brain remodeling and contralesional pyramidal tract plasticity by regulating axonal growth inhibitors and guidance proteins
dc.typeArticle

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