{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T14:54:11Z","timestamp":1794668051170,"version":"4.9.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Central Government Guides Local Scientific and Technological Development Project","award":["Grant No. 2022ZYD0097"],"award-info":[{"award-number":["Grant No. 2022ZYD0097"]}]},{"name":"Sichuan Provincial Health Commission Special Clinical Research Project","award":["Grant No. 23LCYJ034"],"award-info":[{"award-number":["Grant No. 23LCYJ034"]}]},{"name":"Sichuan Medical Youth Innovation Research Project","award":["Grant No. Q21049"],"award-info":[{"award-number":["Grant No. Q21049"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Stroke is a major cause of disability and mortality worldwide, with ischemic stroke (IS) being the most common form. The blood-brain barrier (BBB) plays a critical role in protecting the brain, and its dysfunction after stroke exacerbates neuronal damage. Therefore, restoring BBB integrity is a promising therapeutic strategy. Tirzepatide (TZP), a dual GLP-1 and GIP receptor agonist, has demonstrated neuroprotective effects, but its role in BBB restoration post-stroke remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>This study aims to evaluate the potential of TZP in preventing BBB dysfunction and restoring its integrity in ischemic stroke models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Using a middle cerebral artery occlusion (MCAO) mouse model of ischemic stroke, we assessed the effects of TZP on neurological deficits, BBB permeability, and the expression of tight junction (TJ) proteins, particularly Claudin-1. In vitro, human brain microvascular endothelial cells (HBMVECs) were subjected to oxygen-glucose deprivation\/reperfusion (OGD\/R) to simulate ischemic conditions. The involvement of C\/EBP-\u03b1, a key transcription factor regulating TJ proteins, was also investigated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>TZP treatment significantly improved neurological scores and reduced BBB permeability in MCAO mice. It also restored Claudin-1 expression, which was downregulated in stroke conditions. In vitro, TZP reduced endothelial permeability and enhanced Claudin-1 expression in OGD\/R-treated HBMVECs. Silencing C\/EBP-\u03b1 abolished the protective effects of TZP on both BBB integrity and Claudin-1 expression, indicating that C\/EBP-\u03b1 signaling is crucial for TZP\u2019s action.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>TZP ameliorates BBB dysfunction and protects against ischemic stroke by activating C\/EBP-\u03b1 signaling and restoring Claudin-1-mediated tight junction integrity. These findings suggest that TZP holds promise as a therapeutic agent for stroke, offering a novel strategy for maintaining BBB function and reducing neuronal damage. Further studies are needed to explore the detailed mechanisms underlying TZP\u2019s neuroprotective effects and its clinical potential in stroke therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s10020-025-01312-4","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T07:46:37Z","timestamp":1753256797000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tirzepatide mitigates Stroke-Induced Blood-Brain barrier disruption by modulating Claudin-1 and C\/EBP-\u03b1 pathways"],"prefix":"10.1186","volume":"31","author":[{"given":"Duozi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"issue":"1","key":"1312_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrn1824","volume":"7","author":"NJ Abbott","year":"2006","unstructured":"Abbott NJ, Ronnback L, Hansson E. 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