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

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...

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Autores: Ramos-Cejudo, Jaime, Gutiérrez Fernández, María, Otero Ortega, Laura, Rodríguez-Frutos, Berta, Fuentes Gimeno, Blanca Eulalia, Vallejo-Cremades, María Teresa, Hernanz, Teresa Navarro, Cerdán, Sebastián, Díez Tejedor, Exuperio
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/671186
Acceso en línea:http://hdl.handle.net/10486/671186
https://dx.doi.org/10.1161/STROKEAHA.114.006692
Access Level:acceso abierto
Palabra clave:Brain-derived neurotrophic factor
Endothelin-1
Subcortical stroke
Medicina
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spelling Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic strokeRamos-Cejudo, JaimeGutiérrez Fernández, MaríaOtero Ortega, LauraRodríguez-Frutos, BertaFuentes Gimeno, Blanca EulaliaVallejo-Cremades, María TeresaHernanz, Teresa NavarroCerdán, SebastiánDíez Tejedor, ExuperioBrain-derived neurotrophic factorEndothelin-1Subcortical strokeMedicinaBACKGROUND 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 strokeSupported 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 SpainAmerican Heart AssociationDepartamento de MedicinaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)20152015-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1SMURhttp://purl.org/coar/version/c_71e4c1898caa6e32info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/671186https://dx.doi.org/10.1161/STROKEAHA.114.006692reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6711862026-06-23T12:46:27Z
dc.title.none.fl_str_mv Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
title Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
spellingShingle Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
Ramos-Cejudo, Jaime
Brain-derived neurotrophic factor
Endothelin-1
Subcortical stroke
Medicina
title_short Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
title_full Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
title_fullStr Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
title_full_unstemmed Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
title_sort Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke
dc.creator.none.fl_str_mv Ramos-Cejudo, Jaime
Gutiérrez Fernández, María
Otero Ortega, Laura
Rodríguez-Frutos, Berta
Fuentes Gimeno, Blanca Eulalia
Vallejo-Cremades, María Teresa
Hernanz, Teresa Navarro
Cerdán, Sebastián
Díez Tejedor, Exuperio
author Ramos-Cejudo, Jaime
author_facet Ramos-Cejudo, Jaime
Gutiérrez Fernández, María
Otero Ortega, Laura
Rodríguez-Frutos, Berta
Fuentes Gimeno, Blanca Eulalia
Vallejo-Cremades, María Teresa
Hernanz, Teresa Navarro
Cerdán, Sebastián
Díez Tejedor, Exuperio
author_role author
author2 Gutiérrez Fernández, María
Otero Ortega, Laura
Rodríguez-Frutos, Berta
Fuentes Gimeno, Blanca Eulalia
Vallejo-Cremades, María Teresa
Hernanz, Teresa Navarro
Cerdán, Sebastián
Díez Tejedor, Exuperio
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)
dc.subject.none.fl_str_mv Brain-derived neurotrophic factor
Endothelin-1
Subcortical stroke
Medicina
topic Brain-derived neurotrophic factor
Endothelin-1
Subcortical stroke
Medicina
description 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
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
SMUR
http://purl.org/coar/version/c_71e4c1898caa6e32
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/671186
https://dx.doi.org/10.1161/STROKEAHA.114.006692
url http://hdl.handle.net/10486/671186
https://dx.doi.org/10.1161/STROKEAHA.114.006692
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Heart Association
publisher.none.fl_str_mv American Heart Association
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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