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However, it may contribute to hemorrhagic transformation (HT). The Wnt\/\u03b2-catenin signaling pathway plays an important role in regulating the blood\u2013brain barrier (BBB) formation in the central nervous system. We explored whether glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4) reduces the risk of HT after rtPA treatment via the Wnt\/\u03b2-catenin pathway by using a rat transient middle cerebral artery occlusion (MCAO) model<jats:italic>in vivo<\/jats:italic>and an oxygen\u2013glucose deprivation plus reoxygenation (OGD\/R) model in vitro. Our results showed that EX-4 attenuated neurological deficits, brain edema, infarct volume, BBB disruption, and rtPA-induced HT in ischemic stroke. EX-4 suppressed the production of ROS and the activation of MMP-9 to protect the integrity of the BBB by activating the Wnt\/\u03b2-catenin signaling pathway. PRI-724, a selective inhibitor of \u03b2-catenin, was able to reverse the therapeutic effect of EX-4 in vivo and in vitro. Therefore, our results indicate that the GLP-1R agonist may be a potential therapeutic agent to decrease the risk of rtPA-induced HT after ischemic stroke via the Wnt\/\u03b2-catenin signaling pathway.<\/jats:p>","DOI":"10.1007\/s12035-022-02811-9","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:03:59Z","timestamp":1648760639000},"page":"3649-3664","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["GLP-1R Agonist Exendin-4 Protects Against Hemorrhagic Transformation Induced by rtPA After Ischemic Stroke via the Wnt\/\u03b2-Catenin Signaling Pathway"],"prefix":"10.1007","volume":"59","author":[{"given":"Chengli","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjun","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6971-3461","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"issue":"2","key":"2811_CR1","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1161\/CIRCULATIONAHA.116.023336","volume":"135","author":"JT Kim","year":"2017","unstructured":"Kim JT, Fonarow GC, Smith EE, Reeves MJ, Navalkele DD, Grotta JC et al (2017) Treatment with tissue plasminogen activator in the golden hour and the shape of the 4.5-hour time-benefit curve in the National United States Get With The Guidelines-Stroke Population. 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