國家衛生研究院 NHRI:Item 3990099045/12909
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12909


    Title: Neutralization of lipocalin-2 diminishes stroke-reperfusion injury
    Authors: Wang, G;Weng, YC;Chiang, IC;Huang, YT;Liao, YC;Chen, YC;Kao, CY;Liu, YL;Lee, TH;Chou, WH
    Contributors: Center for Neuropsychiatric Research;Immunology Research Center;Institute of Population Health Sciences
    Abstract: Oxidative stress is a key contributor to the pathogenesis of stroke-reperfusion injury. Neuroinflammatory peptides released after ischemic stroke mediate reperfusion injury. Previous studies, including ours, have shown that lipocalin-2 (LCN2) is secreted in response to cerebral ischemia to promote reperfusion injury. Genetic deletion of LCN2 significantly reduces brain injury after stroke, suggesting that LCN2 is a mediator of reperfusion injury and a potential therapeutic target. Immunotherapy has the potential to harness neuroinflammatory responses and provides neuroprotection against stroke. Here we report that LCN2 was induced on the inner surface of cerebral endothelial cells, neutrophils, and astrocytes that gatekeep the blood-brain barrier (BBB) after stroke. LCN2 monoclonal antibody (mAb) specifically targeted LCN2 in vitro and in vivo, attenuating the induction of LCN2 and pro-inflammatory mediators (iNOS, IL-6, CCL2, and CCL9) after stroke. Administration of LCN2 mAb at 4 h after stroke significantly reduced neurological deficits, cerebral infarction, edema, BBB leakage, and infiltration of neutrophils. The binding epitope of LCN2 mAb was mapped to the β3 and β4 strands, which are responsible for maintaining the integrity of LCN2 cup-shaped structure. These data indicate that LCN2 can be pharmacologically targeted using a specific mAb to reduce reperfusion injury after stroke.
    Date: 2020-08-29
    Relation: International Journal of Molecular Sciences. 2020 Aug 29;21(17):Article number 6253.
    Link to: http://dx.doi.org/10.3390/ijms21176253
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000569595000001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85090181379
    Appears in Collections:[Wen-Hai Chou] Periodical Articles
    [Yu-Li Liu] Periodical Articles
    [Cheng-Yuan Gao] Periodical Articles
    [Others] Periodical Articles

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