Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke

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dc.contributor.author Ramos-Cejudo, Jaime
dc.contributor.author Gutiérrez-Fernández, María
dc.contributor.author Otero-Ortega, Laura
dc.contributor.author Rodríguez-Frutos, Berta
dc.contributor.author Fuentes, Blanca
dc.contributor.author Vallejo-Cremades, María Teresa
dc.contributor.author Hernanz, Teresa Navarro
dc.contributor.author Cerdán, Sebastián
dc.contributor.author Díez-Tejedor, Exuperio
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) es_ES
dc.contributor.other Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) es_ES
dc.date.accessioned 2016-06-01T14:22:15Z
dc.date.available 2016-06-01T14:22:15Z
dc.date.issued 2015-01-01
dc.identifier.citation Stroke 46.1 (2015): 221-8 es_ES
dc.identifier.issn 0039-2499 es_ES
dc.identifier.issn 1524-4628 (on line) es_ES
dc.identifier.uri http://hdl.handle.net/10486/671186
dc.description.abstract BACKGROUND AND PURPOSE: Translational research is beginning to reveal the importance of trophic factors as a therapy for cellular brain repair. The purpose of this study was to analyze whether brain-derived neurotrophic factor (BDNF) administration could mediate oligodendrogenesis and remyelination after white matter injury in subcortical stroke. METHODS: Ischemia was induced in rats by injection of endothelin-1. At 24 hours, 0.4 μg/kg of BDNF or saline was intravenously administered to the treatment and control groups, respectively. Functional evaluation, MRI, and fiber tract integrity on tractography images were analyzed. Proliferation (KI-67) and white matter repair markers (A2B5, 2',3'-cyclic-nucleotide 3'-phosphodiesterase [CNPase], adenomatous polyposis coli [APC], platelet-derived growth factor receptor alpha [PDGFR-α], oligodendrocyte marker O4 [O4], oligodendrocyte transcription factor [Olig-2], and myelin basic protein [MBP]) were analyzed at 7 and 28 days. RESULTS: The BDNF-treated animals showed less functional deficit at 28 days after treatment than the controls (P<0.05). Although T2-MRI did not show differences in lesion size at 7 and 28 days between groups, diffusion tensor imaging tractography analysis revealed significantly better tract connectivity at 28 days in the BDNF group than in the controls (P<0.05). Increased proliferation of oligodendrocyte progenitors was observed in treated animals at 7 days (P<0.05). Finally, the levels of white matter repair markers (A2B5, CNPase, and O4 at 7 days; Olig-2 and MBP at 28 days) were higher in the BDNF group than in the controls (P<0.05). CONCLUSIONS: BDNF administration exerted better functional outcome, oligodendrogenesis, remyelination, and fiber connectivity than controls in rats subjected to subcortical damage in ischemic stroke en_US
dc.description.sponsorship Supported by research grants PS12/01754 (P.I.: EDT), INVICTUS Spanish Neurovascular Network RD12/0014/0006 (BRF and JRC) and Sara Borrell postdoctoral fellowship CD12/00706 (LOO) from the Research Institute Carlos III, Ministry of Science and Innovation of Spain es_ES
dc.format.extent 29 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher American Heart Association en_US
dc.relation.ispartof Stroke en_US
dc.rights © 2014 American Heart Association, Inc en_US
dc.subject.other Brain-derived neurotrophic factor en_US
dc.subject.other Endothelin-1 en_US
dc.subject.other Subcortical stroke en_US
dc.title Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion http://dx.doi.org/10.1161/STROKEAHA.114.006692 en_US
dc.identifier.doi 10.1161/STROKEAHA.114.006692 es_ES
dc.identifier.publicationfirstpage 221 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage 228 es_ES
dc.identifier.publicationvolume 46 es_ES
dc.type.version info:eu-repo/semantics/submittedVersion en_US
dc.rights.accessRights openAccess en
dc.authorUAM Díez Tejedor, Exuperio (258291)
dc.authorUAM Fuentes Gimeno, Blanca Eulalia (262687)


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