{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:00:57Z","timestamp":1774620057855,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2022KY1437"],"award-info":[{"award-number":["2022KY1437"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Ischemic stroke damages the blood\u2013brain barrier (BBB), worsening neuronal injury. Treatments to protect the BBB are limited. We evaluated the neurovascular protective capacity of Kisspeptin\u201054 in ischemic stroke using in\u00a0vivo and in\u00a0vitro models. In\u00a0vivo, mice underwent middle cerebral artery occlusion (MCAO), and cerebral infarct volume, neurological function, and blood\u2013brain barrier (BBB) permeability were evaluated. In\u00a0vitro, human brain microvascular endothelial cells (HBMVECs) were exposed to oxygen\u2013glucose deprivation\/reperfusion (OGD\/R) to assess the effects of Kisspeptin\u201054 on paracellular flux and transendothelial electrical resistance (TEER). Additionally, GATA\u20104 was silenced to investigate its role in mediating protection. Our results showed that cortical ischemia downregulated KISS\u20101 metastasis\u2010suppressor (KISS1, 59% mRNA; 55% protein) and G protein\u2010coupled receptor 54 (GPR54, 54% mRNA; 48% protein), with a 32% decline in circulating Kisspeptin\u201054. Prophylactic Kisspeptin\u201054 reduced cerebral infarct volume by 42%, enhanced neurological performance by 49%, and decreased BBB leakage by 26%, with near\u2010complete occludin recovery. In\u00a0vitro: Kisspeptin\u201054 treatment reduced paracellular flux by 48% and increased transendothelial resistance by 60%. GATA\u20104 silencing abolished Kisspeptin\u201054\u2010induced occludin restoration, increasing permeability by 65% and diminishing barrier resistance by 28%. This study reveals Kisspeptin\u201054 modulates BBB stability via GATA\u20104\u2010driven occludin expression, highlighting the KISS1\/GPR54 pathway as a potential therapeutic target for ischemic stroke.<\/jats:p>","DOI":"10.1111\/cbdd.70134","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T07:47:13Z","timestamp":1748850433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Kisspeptin\u201054 Restores Blood\u2013Brain Barrier Integrity via <scp>GATA<\/scp>\u20104 in Ischemic Stroke"],"prefix":"10.1111","volume":"105","author":[{"given":"Weifeng","family":"Shan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Lishui People's Hospital Wenzhou Medical University Lishui Hospital  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Lishui People's Hospital Wenzhou Medical University Lishui Hospital  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yini","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Lishui People's Hospital Wenzhou Medical University Lishui Hospital  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaomin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Lishui People's Hospital Wenzhou Medical University Lishui Hospital  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minji","family":"You","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Lishui People's Hospital Wenzhou Medical University Lishui Hospital  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9967-9283","authenticated-orcid":false,"given":"Ruijun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Lishui People's Hospital Wenzhou Medical University Lishui Hospital  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00095.2018"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179156"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1915"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/pir.2022-005630"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06430-5"},{"key":"e_1_2_8_7_1","first-page":"2761","article-title":"Mouse Model of Middle Cerebral Artery Occlusion","volume":"48","author":"Chiang T.","year":"2011","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/400_2007_050"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121958"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.12.025"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176821"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.979745"},{"key":"e_1_2_8_13_1","article-title":"An In Vivo Blood\u2010Brain Barrier Permeability Assay in Mice Using Fluorescently Labeled Tracers","volume":"132","author":"Devraj K.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0342"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1182853"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.05.012"},{"issue":"4","key":"e_1_2_8_17_1","first-page":"302","article-title":"Role of GATA\u20104 in Cardiac Development and Remodeling","volume":"39","author":"Jiang S. 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