{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:19:23Z","timestamp":1792819163997,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2023MH023"],"award-info":[{"award-number":["ZR2023MH023"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Project of Shandong University","award":["2021SDUCRCA009"],"award-info":[{"award-number":["2021SDUCRCA009"]}]},{"name":"National Health Commission Capacity Building and Continuing Education Center Nervous"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Microvascular endothelial cells dysfunction can significantly worsen ischaemic stroke outcomes by disrupting tight junctions and increasing the acquisition of adhesion molecules, accelerating blood\u2013brain barrier (BBB) disruption and pro-inflammatory response. The identification of drugs that improve endothelial cell function may be crucial for ischaemic stroke. It has been validated that empagliflozin (EMPA), a novel antidiabetic drug, protects endothelial cells regardless of the diabetic status of the patient. However, the impact of EMPA on stroke outcomes is unclear. We hypothesized that EMPA would exert a beneficial effect on ischaemic stroke outcome by protecting microvascular endothelial cells against tight junction disruption and the increase of adhesion molecules.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Young adult male mice were administered with EMPA or vehicle (dimethyl sulfoxide) daily for 7 days before being subjected to transient middle cerebral artery occlusion (tMCAO). Neurological deficits were evaluated for up to 28 days post-tMCAO. Infarct volume, BBB disruption, and inflammatory status were assessed 1 day after tMCAO.bEnd.3 cells and primary brain microvascular endothelial cells were treated with EMPA or vehicle under oxygen and glucose deprivation\/reperfusion (OGD\/R), and the lactate dehydrogenase release, transendothelial electrical resistance, leakage of fluorescein isothiocyanate-dextran, and tight junction and adhesion molecules proteins were examined. Mechanistic studies probing the effect of EMPA on endothelial cells were conducted by RNA-seq. EMPA treatment before ischaemia markedly improved infarct volume, BBB disruption, and inflammation 1-day post-tMCAO, and further enhanced neurobehavioral function up to 28 days. Pre-treatment of EMPA attenuated endothelial cell dysfunction under OGD\/R conditions. In mechanistic terms, RNA-seq data from isolated cerebral microvessels revealed that the Wnt\/\u03b2-catenin signalling pathway was preserved in the EMPA group, in contrast to the vehicle group. Pre-treatment with EMPA inhibited \u03b2-catenin ubiquitination and promoted \u03b2-catenin translocation from the cytoplasm to the nucleus to improve endothelial cell function. Importantly, the \u03b2-catenin inhibitor XAV-939 eliminated this protective function of EMPA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>EMPA administration before tMCAO attenuated ischaemia\/reperfusion-induced BBB disruption and inflammation via \u03b2-catenin-mediated protection of cerebral microvascular endothelial cells. Therefore, EMPA shows potential for improving stroke outcomes as an adjunctive preventive strategy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf026","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T21:36:07Z","timestamp":1743370567000},"page":"788-802","source":"Crossref","is-referenced-by-count":19,"title":["Pre-ischaemic empagliflozin treatment attenuates blood\u2013brain barrier disruption via \u03b2-catenin mediated protection of cerebral endothelial cells"],"prefix":"10.1093","volume":"121","author":[{"given":"Guohao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 ,","place":["China"]},{"name":"Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 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