Document Detail


Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia.
MedLine Citation:
PMID:  23149556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Francisco J Ortega; Jukka Jolkkonen; Nicole Mahy; Manuel J Rodríguez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-04-19     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  356-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / antagonists & inhibitors,  metabolism
Animals
Antigens, Nuclear / metabolism
Brain Ischemia* / drug therapy,  metabolism,  pathology,  physiopathology
Cell Movement / drug effects
Corpus Striatum / metabolism,  pathology,  physiopathology
Dose-Response Relationship, Drug
Glyburide* / pharmacokinetics,  pharmacology
Hippocampus / metabolism,  pathology,  physiopathology
Hypoglycemic Agents* / pharmacokinetics,  pharmacology
Male
Maze Learning / drug effects
Microglia / metabolism,  pathology
Microtubule-Associated Proteins / metabolism
Neovascularization, Physiologic / drug effects
Nerve Tissue Proteins / metabolism
Neurogenesis / drug effects*
Neuropeptides / metabolism
Potassium Channels, Inwardly Rectifying / antagonists & inhibitors,  metabolism
Rats
Rats, Wistar
Receptors, Drug / antagonists & inhibitors,  metabolism
Recovery of Function / drug effects*
Sulfonylurea Receptors
Time Factors
Chemical
Reg. No./Substance:
0/Abcc8 protein, rat; 0/Antigens, Nuclear; 0/Hypoglycemic Agents; 0/Kir6.2 channel; 0/Microtubule-Associated Proteins; 0/Nerve Tissue Proteins; 0/NeuN protein, rat; 0/Neuropeptides; 0/Potassium Channels, Inwardly Rectifying; 0/Receptors, Drug; 0/Sulfonylurea Receptors; 0/doublecortin protein; SX6K58TVWC/Glyburide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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