|Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia.|
|PMID: 23149556 Owner: NLM Status: MEDLINE|
|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.|
|Francisco J Ortega; Jukka Jolkkonen; Nicole Mahy; Manuel J Rodríguez|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-11-14|
|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|
|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|
|Languages: eng Pagination: 356-64 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
ATP-Binding Cassette Transporters
antagonists & inhibitors,
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
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
Receptors, Drug / antagonists & inhibitors, metabolism
Recovery of Function / drug effects*
|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|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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