Glibenclamide pretreatment attenuates early hematoma expansion of warfarin-associated intracerebral hemorrhage in rats by alleviating perihematomal blood-brain barrier dysfunction  

作　　者：Zongwei Zeng Liang Liang Zhou Feng Peiwen Guo Xiaoke Hao Jishu Xian Hua Feng Yujie Chen Zhi Chen 

机构地区：[1]Department of Neurosurgery and State Key Laboratory of Trauma,Burn and Combined Injury,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [2]Department of Neurosurgery,The 945Th Hospital of PLA,Yaan,Sichuan Province 625099,China [3]Department of Rehabilitation,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [4]Chongqing Key Laboratory of Precision Neuromedicine and Neuroregeneration,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [5]Chongqing Clinical Research Center for Neurosurgery,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China

出　　处：《Chinese Neurosurgical Journal》2024年第1期8-19,共12页中华神经外科杂志（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81771241 to Zhi Chen);Third Military Medical University(No.XZ-2019-505-002 to Zhi Chen);Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science&Technology Bureau,No.2023GGXM003 to Hua Feng)

摘　　要：Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently,especially in warfarin-associated intracerebral hemorrhage(W-ICH).In the present study,we employ the warfarin-associated intracerebral hemorrhage(W-ICH)rat model,to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage,hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage.Methods In the present study,we tested whether glibenclamide,a common hypoglycemic drug,could attenuate hematoma expansion in a rat model of W-ICH.Hematoma expansion was evaluated using magnetic resonance imaging;brain injury was evaluated by brain edema and neuronal death;and functional outcome was evaluated by neurological scores.Then blood-brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein.Results The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH,thus mitigating brain edema and neuronal death and promoting neurological function recovery,which may benefit from alleviating blood-brain barrier disruption by suppressing matrix metallopeptidase-9.Conclusions The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH.

关 键 词：Intracerebral hemorrhage WARFARIN GLIBENCLAMIDE Hematoma expansion Blood-brain barrier Matrix metallopeptidase-9 

分 类 号：R743[医药卫生—神经病学与精神病学]