title: Protective effect of treatment with low-dose gliclazide in a model of middle cerebral artery occlusion and reperfusion in rats.
abstract: The aim of this study was to explore the expression of sulfonylurea receptor 1 (SUR1), the regulatory subunit of the NCCa-ATP channel, and to investigate the protective effects of gliclazide following middle cerebral artery occlusion (MCAO)/reperfusion in male Wistar rats. Adult rats underwent 2h of the left MCAO using the intraluminal thread technique before reperfusion. The core areas of the infarct at different reperfusion time points were examined for the mRNA level and protein expression of SUR1 using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting respectively. Gliclazide was administered intravenously into the right jugular vein for 12h simultaneously with the reperfusion. The number of apoptotic cells was determined using the TUNEL assay. The neurological functional deficits were evaluated using Bederson׳s test, and the cerebral infarction volume was visualized with TTC staining. We found up-regulation of SUR1 mRNA and protein levels in ischemic infarct tissues after reperfusion following MCAO, and SUR1 mRNA and protein were maximally upregulated 8-12h after a 2-hour ischemia. The treatment with low-dose of gliclazide reduced the total number of TUNEL-positive cells, the neurological functional deficits and the brain infarct volume. These results suggest that the SUR1-regulated NCCa-ATP channel may be associated with MCAO/reperfusion injury and the infarct-reducing effects of intravenous treatment with gliclazide may be due, in part, to the blocked upregulation of SUR1 expression, the decreased infarct size and the reduced apoptosis in the ischemia-reperfusion brain.
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu, Sichuan 610041, China. Electronic address: tanfang721@126.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Tan
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu, Sichuan 610041, China. Electronic address: lihua2166@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medical Cell Biology and Medical Genetics, Luzhou Medical College, No. 1, 1st Section of Xianglin Road, Longmatan District, Luzhou, Sichuan 646000, China. Electronic address: luyimamingyi@163.com.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu, Sichuan 610041, China. Electronic address: yerongyu@scu.edu.cn.
authors.forename: Yerong
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D005907:Gliclazide / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007262:Infusions, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D064233:Sulfonylurea Receptors / Q000378:metabolism
chemical_list: C577509:Abcc8 protein, rat; D001786:Blood Glucose; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D064233:Sulfonylurea Receptors; D005907:Gliclazide
keywords: Gliclazide; Middle cerebral artery occlusion; NC(Ca-ATP) channel; Neuroprotection; Reperfusion; Sulfonylurea receptor