Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage.
Brain edema following intracerebral hemorrhage (ICH) causes severe secondary brain injury, and no efficient pharmacological preventions are available. The present study was designed to demonstrate the neuroprotective effects of glibenclamide on brain edema and key factors of the blood-brain barrier (BBB). The study was divided into two parts. First, we utilized an autoblood-induced rat model to investigate the expression of sulfonylurea receptor 1 (Sur1). Second, rats were randomized into sham, vehicle, and glibenclamide groups. Neurological scores, brain water content, Evans blue extravasation, Morris water maze test, western blots, and immunofluorescence were used to study the effects of glibenclamide. The expression of the Sur1-Trpm4 channel but not the Sur1-KATP channel was increased in the perihematomal tissue following ICH. Glibenclamide administration significantly decreased the brain water content, restored the BBB, and reduced the expression of MMPs. In addition, glibenclamide improved long-term cognitive deficits following ICH. Glibenclamide protected BBB integrity and improved neurological outcomes after ICH by inhibiting the Sur1-Trpm4 channel, which reduces the expression of MMPs and thereby increases BBB tight-junction protein levels. Glibenclamide may have potential to protect the BBB after ICH.
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Bing
B
Jiang
Department of Neurosurgery, Nanchong Central Hospital, Sichuan, 637000, China.
Lin
L
Li
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Qianwei
Q
Chen
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Yihao
Y
Tao
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Liming
L
Yang
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Bo
B
Zhang
Department of Neurosurgery, School of Medicine, Loma Linda University, Loma Linda, CA, USA.
John H
JH
Zhang
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Hua
H
Feng
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Zhi
Z
Chen
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China. tangjun@tmmu.edu.cn.
Jun
J
Tang
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People's Republic of China. gangzhu6666@sina.com.
Gang
G
Zhu
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000008:administration & dosage*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D062793:Occludin / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064233:Sulfonylurea Receptors / Q000819:agonists* / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D000099161:Kcnj11 Channel
D001786:Blood Glucose; D005905:Glyburide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D062793:Occludin; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; D050053:TRPM Cation Channels; D062826:Zonula Occludens-1 Protein; D000099161:Kcnj11 Channel; C577509:Abcc8 protein, rat; C568987:Ocln protein, rat; C500239:TRPM4 protein, rat; C569044:Tjp1 protein, rat
BBB; Glibenclamide; Intracerebral hemorrhage; MMPs; Sur1