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NB-3 expression in endothelial cells contributes to the maintenance of blood brain barrier integrity in a mouse high-altitude cerebral edema model.

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机构： [1]Beijing Institute of Basic Medical Sciences, Beijing 100850, China [2]Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China [3]College of Life Sciences, Anhui Medical University, Hefei 230032, China [4]School of Pharmaceutical Sciences, University of South China, Hengyang 421001, China [5]Xuanwu Hospital, Capital Medical University, Beijing 100053, China

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关键词： NB-3 Endothelial cells Blood-brain barrier High altitude cerebral edema

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NB-3, a member of the contactin/F3 subgroup in the immunoglobulin superfamily, plays an important role in neural development and injury recovery. The blood brain barrier (BBB) is typically involved in the pathophysiology of neural disorders, such as hypoxic-ischemic brain injury. Our previous research found that NB-3 protects against brain damage in a mouse stroke model. However, its role in high-altitude disorders caused by hypobaric hypoxia exposure remains unknown. In the present study, we found that NB-3 was expressed in brain microvascular endothelial cells (BMECs) and responded to hypoxia stimulation. Conditional knockout of NB-3 in endothelial cells increased BBB leakage and downregulated tight junction proteins in vivo. NB-3 deficiency promoted the downregulation of tight junction proteins under Lipopolysaccharide (LPS)/hypoxia stimulation. Conversely, overexpression or supplementation with NB-3 alleviated endothelial barrier injuries. Transcriptome sequencing showed that NB-3 regulated various cell attachment genomic changes, including the Notch signaling pathway. Blocking the Notch signaling pathway increased VEGF/VEGFR2 pathway activation induced by LPS/hypoxia. Collectively, we present evidence that NB-3 plays key roles in maintaining BBB integrity under high-altitude cerebral edema conditions.Copyright © 2022. Published by Elsevier Inc.

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出版当年[2021]版：

大类 | 2 区医学

小类 | 2 区神经科学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区神经科学

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出版当年[2020]版：

Q2 NEUROSCIENCES

最新[2023]版：

Q1 NEUROSCIENCES

影响因子： 4.6 最新[2023版] 4.8 最新五年平均 5.33 出版当年[2020版] 5.34 出版当年五年平均 4.691 出版前一年[2019版] 5.62 出版后一年[2021版]

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第一作者机构： [1]Beijing Institute of Basic Medical Sciences, Beijing 100850, China

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通讯机构： [1]Beijing Institute of Basic Medical Sciences, Beijing 100850, China [2]Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China [3]College of Life Sciences, Anhui Medical University, Hefei 230032, China [4]School of Pharmaceutical Sciences, University of South China, Hengyang 421001, China [*1]No.27, Taiping Road, Haidian District, Beijing 100850, China.

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NB-3 expression in endothelial cells contributes to the maintenance of blood brain barrier integrity in a mouse high-altitude cerebral edema model.

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