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  

作　　者：Heling Chu Zidan Gao Chuyi Huang Jing Dong Yuping Tang Qiang Dong 

机构地区：[1]Department of Neurology,Huashan Hospital,State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200040,China [2]Department of Neurology,North Huashan Hospital,Fudan University,Shanghai 201907,China [3]Department of Neurology,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China [4]Department of Neurology,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120,China

出　　处：《Neuroscience Bulletin》2020年第11期1369-1380,共12页神经科学通报（英文版）

基　　金：grants from the National Natural Science Foundation of China(81500998 and 81901102);the Science and Technology Commission of Shanghai Municipality(16140903200);Shanghai Sixth People’s Hospital Medical Group(2017LY01);the Research Fund of Shanghai Tongren Hospital,Shanghai Jiaotong University School of Medicine(TRYJ201701);the Research Fund of North Huashan Hospital,Fudan University(HSBY2019004)。

摘　　要：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 

分 类 号：R743.34[医药卫生—神经病学与精神病学]