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

Authors: Ortega, Francisco J  Jolkkonen, Jukka  Mahy, Nicole  Rodríguez, Manuel J 
Citation: Ortega FJ, etal., J Cereb Blood Flow Metab. 2013 Mar;33(3):356-64. doi: 10.1038/jcbfm.2012.166. Epub 2012 Nov 14.
Pubmed: (View Article at PubMed) PMID:23149556
DOI: Full-text: DOI:10.1038/jcbfm.2012.166

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 0.6¿µg) 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.


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CRRD ID: 12790979
Created: 2017-02-23
Species: All species
Last Modified: 2017-02-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.