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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.contributor.authorBeker, Merve
dc.contributor.authorCaglayan, Ahmet B.
dc.contributor.authorBeker, Mustafa C.
dc.contributor.authorAltunay, Serdar
dc.contributor.authorKaracay, Reyda
dc.contributor.authorDalay, Arman
dc.contributor.authorAltintas, Mehmet O.
dc.contributor.authorKÖSE, GAMZE
dc.contributor.authorHermann, Dirk M.
dc.contributor.authorKILIÇ, ERTUĞRUL
dc.contributor.institutionauthorBEKER, MERVE
dc.date.accessioned2020-10-29T15:36:18Z
dc.date.available2020-10-29T15:36:18Z
dc.date.issued2020-09-01T00:00:00Z
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.sponsorshipBezmiâlem Vakıf Üniversitesi
dc.identifier.citationBeker M., Caglayan A. B. , Beker M. C. , Altunay S., Karacay R., Dalay A., Altintas M. O. , KÖSE G., Hermann D. M. , KILIÇ E., -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, cilt.331, 2020
dc.identifier.doi10.1016/j.expneurol.2020.113364
dc.identifier.pubmed32454038
dc.identifier.scopus85085621108
dc.identifier.urihttp://hdl.handle.net/20.500.12645/25610
dc.identifier.wosWOS:000566790500001
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
dspace.entity.typePublication
local.avesis.id37f11fb2-0b49-4a68-93f6-eaca4985f952
local.publication.isinternational1
relation.isAuthorOfPublication6f8a3a29-68af-47b4-b206-bbc6051b00f5
relation.isAuthorOfPublication.latestForDiscovery6f8a3a29-68af-47b4-b206-bbc6051b00f5
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