Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia

Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of...

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Detalhes bibliográficos
Autores: Ortega González, Fco. Javier, Jolkkonen, Jukka, Mahy Gehenne, Josette Nicole, Rodríguez Allué, Manuel José
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2012
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/44837
Acesso em linha:https://hdl.handle.net/2445/44837
Access Level:Acceso aberto
Palavra-chave:Isquèmia cerebral
Micròglia
Regeneració del sistema nerviós
Cerebral ischemia
Microglia
Nervous system regeneration
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spelling Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemiaOrtega González, Fco. JavierJolkkonen, JukkaMahy Gehenne, Josette NicoleRodríguez Allué, Manuel JoséIsquèmia cerebralMicrògliaRegeneració del sistema nerviósCerebral ischemiaMicrogliaNervous system regenerationGlibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.International Society for Cerebral Blood Flow and Metabolism2012info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/44837Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: http://dx.doi.org/10.1038/jcbfm.2012.166Journal of Cerebral Blood Flow and Metabolism, 2013, vol. 33, num. 3, p. 356-364http://dx.doi.org/10.1038/jcbfm.2012.166(c) Ortega González, Fco. Javier et al., 2013info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/448372026-05-27T06:46:51Z
dc.title.none.fl_str_mv Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
title Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
spellingShingle Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
Ortega González, Fco. Javier
Isquèmia cerebral
Micròglia
Regeneració del sistema nerviós
Cerebral ischemia
Microglia
Nervous system regeneration
title_short Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
title_full Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
title_fullStr Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
title_full_unstemmed Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
title_sort Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia
dc.creator.none.fl_str_mv Ortega González, Fco. Javier
Jolkkonen, Jukka
Mahy Gehenne, Josette Nicole
Rodríguez Allué, Manuel José
author Ortega González, Fco. Javier
author_facet Ortega González, Fco. Javier
Jolkkonen, Jukka
Mahy Gehenne, Josette Nicole
Rodríguez Allué, Manuel José
author_role author
author2 Jolkkonen, Jukka
Mahy Gehenne, Josette Nicole
Rodríguez Allué, Manuel José
author2_role author
author
author
dc.subject.none.fl_str_mv Isquèmia cerebral
Micròglia
Regeneració del sistema nerviós
Cerebral ischemia
Microglia
Nervous system regeneration
topic Isquèmia cerebral
Micròglia
Regeneració del sistema nerviós
Cerebral ischemia
Microglia
Nervous system regeneration
description Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/44837
url https://hdl.handle.net/2445/44837
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1038/jcbfm.2012.166
Journal of Cerebral Blood Flow and Metabolism, 2013, vol. 33, num. 3, p. 356-364
http://dx.doi.org/10.1038/jcbfm.2012.166
dc.rights.none.fl_str_mv (c) Ortega González, Fco. Javier et al., 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Ortega González, Fco. Javier et al., 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv International Society for Cerebral Blood Flow and Metabolism
publisher.none.fl_str_mv International Society for Cerebral Blood Flow and Metabolism
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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