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

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Chinese Neurosurgical Journal 2024年第1期10卷 8-19页

作者： Zongwei Zeng Liang Liang Zhou Feng Peiwen Guo Xiaoke Hao Jishu Xian Hua Feng Yujie Chen Zhi Chen Department of Neurosurgery and State Key Laboratory of Trauma Burn and Combined InjurySouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Neurosurgery The 945Th Hospital of PLAYaanSichuan Province 625099China Department of Rehabilitation Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing Key Laboratory of Precision Neuromedicine and Neuroregeneration Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing Clinical Research Center for Neurosurgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

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

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Relationship Between hematoma expansion Induced by Hypertension and Hyperglycemia and Blood-brain Barrier Disruption in Mice and Its Possible Mechanism:Role of Aquaporin-4 and Connexin43

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Neuroscience Bulletin 2020年第11期36卷 1369-1380页

作者： Heling Chu Zidan Gao Chuyi Huang Jing Dong Yuping Tang Qiang Dong Department of Neurology Huashan HospitalState Key Laboratory of Medical NeurobiologyFudan UniversityShanghai 200040China Department of Neurology North Huashan HospitalFudan UniversityShanghai 201907China Department of Neurology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Neurology Shanghai East HospitalTongji University School of MedicineShanghai 200120China

We aimed to select an optimized hematoma expansion(HE)model and investigate the possible mechanism of blood-brain barrier(BBB)damage in mice.The results showed that HE occurred in the group with hypertension combined with hyperglycemia(HH-HE)from3 to 72 h after intracerebral hemorrhage;this was accompanied by neurological deficits and hardly influenced the survival rate.The receiver operating characteristic curve suggested the criterion for this model was hematoma volume expansion≥45.0%.Meanwhile,HH-HE aggravated BBB disruption.A protector of the BBB reduced HH-HE,while a BBB disruptor induced a further HH-HE.Aquaporin-4(AQP4)knock-out led to larger hematoma volume and more severe BBB disruption.Furthermore,hematoma volume and BBB disruption were reduced by multiple connexin43(Cx43)inhibitors in the wild-type group but not in the AQP4 knock-out group.In conclusion,the optimized HE model is induced by hypertension and hyperglycemia with the criterion of hematoma volume expanding≥45.0%.HH-HE leads to BBB disruption,which is dependent on AQP4 and Cx43.

关键词： Intracerebral hemorrhage hematoma expansion Animal model Blood-brain barrier Aquaporin-4 Connexin43

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A New Method for Predicting Intracerebral hematoma expansion:Volume Difference Measured by ABC/2 and Slicer Software

A New Method for Predicting Intracerebral Hematoma Expansion...

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第十三届中国医师协会神经外科医师年会

作者： Wu Gang Liu Ruen Department of Neurosurgery Peking University People’s Hospital

Back ground:Intracerebral hemorrhage has a tendency to enlarge over the time course of disease.Accurate predicting the enlargement of hematoma is not easy,but significantly helpful for clinical management of the patients.This study is aimed to provide a new method to predict hematoma expansion.Methods:Initial CT scan images of 128 patients with spontaneous intracerebral hematoma were analyzed.hematoma volumes were measured with ABC/2 method and 3 D slicer software.The difference of hematoma volume evaluated by the two methods was used to predict hematoma expansion in two criterions（≥6.0 cm3 growth;≥12.5 cm3 growth）,compared to hematoma shape categories.Results:The hematoma volume initially measured by ABC/2 and 3 D slicer was 21.4±16.4 cm3,17.7±14.0 cm3 respectively.The hematoma volume measured by ABC/2 method was bigger than that by 3 D slicer（t=11.869,P＜0.001）.The hematoma volume difference measured by the two methods was correlated with the volume of hematoma growth in different hematoma shape groups respectively（R=0.628,R=0.603 and R=0.591）.The area under curve of volume difference is significantly bigger than that of hematoma shape categories in two situations（hematoma expansion,≥6.0 cm3,P=0.027;≥12.5 cm3,P=0.020）.Conclusions:Comparing to hematoma shape categories,the difference of volume measured by ABC/2 and 3 D slicer could better predict the hematoma expansion.

关键词： intracerebral hemorrhage hematoma expansion hematoma shape category 3D slicer

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