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oai:recercat.cat:2445/448372025-12-05T09:21:36Zcom_2072_1057col_2072_478799col_2072_478917

Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia Ortega González, Fco. Javier Jolkkonen, Jukka Mahy Gehenne, Josette Nicole Rodríguez Allué, Manuel José Isquèmia cerebral Micròglia Regeneració del sistema nerviós Cerebral ischemia Microglia Nervous system regeneration 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. 2013-07-16T11:05:33Z 2014-05-14T22:02:11Z 2012-11-14 2013-07-16T10:05:45Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 0271-678X https://hdl.handle.net/2445/44837 617153 23149556 eng 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 (c) Ortega González, Fco. Javier et al., 2013 info:eu-repo/semantics/openAccess 9 p. application/pdf International Society for Cerebral Blood Flow and Metabolism Articles publicats en revistes (Ciències Fisiològiques)