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Inhibition of NOX4/ROS Suppresses Neuronal and Blood-Brain Barrier Injury by Attenuating Oxidative Stress After Intracerebral Hemorrhage.

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机构： [1]Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, China. [2]Department of Neurosurgery, The First Affiliated Hospital of University of South China, Hengyang, China. [3]Department of Neurosurgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. [4]Department of Neurosurgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. [5]Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. [6]Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

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关键词： ICH=intracerebral hemorrhage oxidative stress blood-brain barrier apoptosis NOX4 NADPH oxidase

摘要：

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder that can effectively induce oxidative stress responses. NADPH oxidase 4 (NOX4) is a member of the NOX family of oxidases. It is expressed in the brain normally and involved in cell signal transduction and the removal of harmful substances. In some pathological conditions, it mediates inflammation and the aging of cells. However, few studies have focused on whether NOX4 is involved in brain injury caused by ICH. Therefore, this study aimed to clarify the role of NOX4 in the pathological process that occurs after ICH and the potential mechanism underlying its role. A rat model of ICH was established by the injection of collagenase type IV, and the expression of NOX4 was then determined. Further, siRNA-mediated protein expression knockdown technology was used for NOX4 knockdown, and western immunoblotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and other molecular biological techniques were performed to assess the effects of NOX4 knockdown. Neurobiological scoring, brain water content determination, and other brain injury detection methods were also performed to assess the role of NOX4 following ICH. We found that the expression of NOX4 increased in the brains of rats after ICH, and that it was mainly expressed in neurons, astrocytes, vascular endothelial cells and microglia. Following NOX4 knockdown, the level of oxidative stress in the brain decreased considerably, the neurobehavioral scores improved, the levels of neuronal apoptosis reduced markedly, and the impairment of blood-brain barrier function was significantly ameliorated in rats with ICH. In conclusion, this study suggests that NOX4 expression is upregulated after ICH, which may cause an imbalance in the oxidative stress of relevant cells in the brain, leading to subsequent apoptosis of neurons and damage to the blood-brain barrier due to secondary brain injury following ICH. Copyright © 2020 Xie, Hong, Ding, Jiang, Zheng, Xie, Tian and Chen.

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出版当年[2019]版：

大类 | 2 区医学

小类 | 2 区神经科学

最新[2025]版：

大类 | 3 区医学

小类 | 3 区神经科学

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出版当年[2018]版：

Q2 NEUROSCIENCES

最新[2023]版：

Q2 NEUROSCIENCES

影响因子： 4.2 最新[2023版] 5.1 最新五年平均 3.9 出版当年[2018版] 4.917 出版当年五年平均 4.3 出版前一年[2017版] 3.921 出版后一年[2019版]

第一作者：

第一作者机构： [1]Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, China.

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通讯作者：

通讯机构： [1]Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, China. [6]Department of Neurosurgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

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Inhibition of NOX4/ROS Suppresses Neuronal and Blood-Brain Barrier Injury by Attenuating Oxidative Stress After Intracerebral Hemorrhage.

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