Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats

Studies from a single laboratory have shown that in rodent models of permanent stroke, administration of the sulfonylurea glibenclamide (Glib) is highly effective in reducing edema, mortality, and lesion volume. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends that new acute treat...

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Main Authors: Bushra Wali, Tauheed Ishrat, Fahim Atif, Fang Hua, Donald G. Stein, Iqbal Sayeed
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Stroke Research and Treatment
Online Access:http://dx.doi.org/10.1155/2012/460909
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author Bushra Wali
Tauheed Ishrat
Fahim Atif
Fang Hua
Donald G. Stein
Iqbal Sayeed
author_facet Bushra Wali
Tauheed Ishrat
Fahim Atif
Fang Hua
Donald G. Stein
Iqbal Sayeed
author_sort Bushra Wali
collection DOAJ
description Studies from a single laboratory have shown that in rodent models of permanent stroke, administration of the sulfonylurea glibenclamide (Glib) is highly effective in reducing edema, mortality, and lesion volume. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends that new acute treatments for ischemic stroke to be replicated across different laboratories. Accordingly, we examined the effect of low-dose Glib in a permanent suture occlusion model of stroke. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO) followed by an initial intraperitoneal injection of Glib (10 μg/kg) and the start of a constant infusion (200 ng/h) via miniosmotic pump at the onset of ischemia. Functional deficits were assessed by Neurological Severity Score (NSS) and grip-strength meter at 24 and 48 h after pMCAO. Glib-treated rats showed a significant reduction in infarct volume, lower NSS, and less hemispheric swelling compared to vehicle. Grip strength was decreased significantly in pMCAO rats compared to shams and significantly improved by treatment with Glib. Taken together, these data indicate that Glib has strong neuroprotective effects following ischemic stroke and may warrant further testing in future clinical trials for human stroke.
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spelling doaj-art-eb14878b6c2a4c76b1e3c70e9e1a311a2025-08-20T02:22:02ZengWileyStroke Research and Treatment2090-81052042-00562012-01-01201210.1155/2012/460909460909Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in RatsBushra Wali0Tauheed Ishrat1Fahim Atif2Fang Hua3Donald G. Stein4Iqbal Sayeed5Department of Emergency Medicine, School of Medicine Emory University, Atlanta, GA 30322, USADepartment of Emergency Medicine, School of Medicine Emory University, Atlanta, GA 30322, USADepartment of Emergency Medicine, School of Medicine Emory University, Atlanta, GA 30322, USADepartment of Emergency Medicine, School of Medicine Emory University, Atlanta, GA 30322, USADepartment of Emergency Medicine, School of Medicine Emory University, Atlanta, GA 30322, USADepartment of Emergency Medicine, School of Medicine Emory University, Atlanta, GA 30322, USAStudies from a single laboratory have shown that in rodent models of permanent stroke, administration of the sulfonylurea glibenclamide (Glib) is highly effective in reducing edema, mortality, and lesion volume. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends that new acute treatments for ischemic stroke to be replicated across different laboratories. Accordingly, we examined the effect of low-dose Glib in a permanent suture occlusion model of stroke. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO) followed by an initial intraperitoneal injection of Glib (10 μg/kg) and the start of a constant infusion (200 ng/h) via miniosmotic pump at the onset of ischemia. Functional deficits were assessed by Neurological Severity Score (NSS) and grip-strength meter at 24 and 48 h after pMCAO. Glib-treated rats showed a significant reduction in infarct volume, lower NSS, and less hemispheric swelling compared to vehicle. Grip strength was decreased significantly in pMCAO rats compared to shams and significantly improved by treatment with Glib. Taken together, these data indicate that Glib has strong neuroprotective effects following ischemic stroke and may warrant further testing in future clinical trials for human stroke.http://dx.doi.org/10.1155/2012/460909
spellingShingle Bushra Wali
Tauheed Ishrat
Fahim Atif
Fang Hua
Donald G. Stein
Iqbal Sayeed
Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats
Stroke Research and Treatment
title Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats
title_full Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats
title_fullStr Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats
title_full_unstemmed Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats
title_short Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats
title_sort glibenclamide administration attenuates infarct volume hemispheric swelling and functional impairments following permanent focal cerebral ischemia in rats
url http://dx.doi.org/10.1155/2012/460909
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