Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/44837
Title: | Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia |
Author: | Ortega González, Fco. Javier Jolkkonen, Jukka Mahy Gehenne, Josette Nicole Rodríguez Allué, Manuel José |
Keywords: | Isquèmia cerebral Micròglia Regeneració del sistema nerviós Cerebral ischemia Microglia Nervous system regeneration |
Issue Date: | 14-Nov-2012 |
Publisher: | International Society for Cerebral Blood Flow and Metabolism |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1038/jcbfm.2012.166 |
It is part of: | Journal of Cerebral Blood Flow and Metabolism, 2013, vol. 33, num. 3, p. 356-364 |
URI: | http://hdl.handle.net/2445/44837 |
Related resource: | http://dx.doi.org/10.1038/jcbfm.2012.166 |
ISSN: | 0271-678X |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
617153.pdf | 1.67 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.