{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:02:15Z","timestamp":1791522135902,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T00:00:00Z","timestamp":1598659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI, NP-108-PP-09"],"award-info":[{"award-number":["NHRI, NP-108-PP-09"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Government S &amp; T grant","award":["109-1901-01-19-07"],"award-info":[{"award-number":["109-1901-01-19-07"]}]},{"name":"Ministry of Science and Technology","award":["MOST-108-2320-B-400-015-MY3"],"award-info":[{"award-number":["MOST-108-2320-B-400-015-MY3"]}]},{"DOI":"10.13039\/100010254","name":"Kent State University","doi-asserted-by":"publisher","award":["start-up fund"],"award-info":[{"award-number":["start-up fund"]}],"id":[{"id":"10.13039\/100010254","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013brain 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 \u03b23 and \u03b24 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.<\/jats:p>","DOI":"10.3390\/ijms21176253","type":"journal-article","created":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T06:06:22Z","timestamp":1598767582000},"page":"6253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Neutralization of Lipocalin-2 Diminishes Stroke-Reperfusion Injury"],"prefix":"10.3390","volume":"21","author":[{"given":"Guona","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chinn","family":"Weng","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chen","family":"Chiang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Institute of Population Health Sciences, National Health Research Institutes, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yuan","family":"Kao","sequence":"additional","affiliation":[{"name":"Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsong-Hai","family":"Lee","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hai","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA"},{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e259","DOI":"10.1016\/S2214-109X(13)70089-5","article-title":"Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990\u20132010: Findings from the Global Burden of Disease Study 2010","volume":"1","author":"Krishnamurthi","year":"2013","journal-title":"Lancet Glob. 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