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Profiling of plasma extracellular vesicles (EVs) revealed a higher abundance of circMagi1 in patients with acute ischemic stroke compared with healthy controls. This upregulation was recapitulated in the ischemic mouse brain, where cell\u2010type\u2010resolved analyses identified injured neurons as a primary source of circMagi1\u2010containing EVs that accumulate in endothelial cells. Mechanistically, endothelial circMagi1 binds ANXA2 and enhances its engagement with TRIM65, thereby promoting TRIM65\u2010mediated ANXA2 ubiquitination and proteasomal degradation and restraining angiogenesis. To therapeutically target this axis in vivo, treatment with siCircMagi1\u2010RVG\u2010EVs was initiated on post\u2010stroke day 1 and maintained thereafter, while siTrim65\u2010Ang2\u2010EVs were introduced from either day 1 or day 9. Among the schedules tested, adding siTrim65\u2010Ang2\u2010EVs from day 9 was associated with greater neurovascular recovery than sustained circMagi1\u2010targeted treatment alone or co\u2010initiation on day 1. Together, these findings delineate a vesicle\u2010mediated signaling axis linking neuronal injury to impaired vascular repair and support further evaluation of delayed TRIM65 inhibition during sustained circMagi1 suppression.<\/jats:p>","DOI":"10.1002\/advs.77808","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:21:52Z","timestamp":1792128112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuron\u2010Derived Vesicular circMagi1 Restrains Vascular Repair After Ischemic Stroke by Promoting TRIM65\u2010Mediated ANXA2 Degradation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-9294","authenticated-orcid":false,"given":"Youkun","family":"Bi","sequence":"first","affiliation":[{"name":"Institute of Biomedical Research Henan Academy of Sciences  Zhengzhou China"},{"name":"State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics Chinese Academy of Sciences  Beijing China"},{"name":"Faculty of Synthetic Biology Shenzhen University of Advanced Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2684-0024","authenticated-orcid":false,"given":"Qun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-348X","authenticated-orcid":false,"given":"Baohua","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning Normal University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Yuan Sheng Biotechnology Ltd.  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