{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:15:29Z","timestamp":1791573329853,"version":"4.3.4"},"reference-count":192,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Brain microvascular endothelial cells (BMECs) constitute the core component of the Blood-Brain Barrier (BBB), whose structural and functional integrity is crucial for maintaining central nervous system homeostasis. In recent years, ferroptosis\u2014a novel iron-dependent lipid peroxidation-driven cell death pathway\u2014has been demonstrated to play a pivotal role in secondary brain injury following stroke. However, current research predominantly focuses on ferroptosis in neurons and glial cells, with insufficient attention given to the mechanisms underlying BMEC ferroptosis in stroke pathogenesis. This review systematically examines the pivotal role of BMEC ferroptosis in the development of both ischemic and hemorrhagic strokes, elucidating its multiple pathways for exacerbating brain injury: compromising BBB integrity, triggering vasogenic cerebral edema, intensifying neuroinflammation, and promoting hemorrhagic transformation. The article highlights the molecular mechanisms of signaling pathways\u2014including Meg3\/p53\/GPX4, TEAD1\/MMP3, SESN2\/System Xc\u2212\/GPX4, and SP1\/TNFSF9\/SLC3A2\u2014in regulating BMEC ferroptosis. It summarizes multidimensional therapeutic strategies encompassing iron chelators, genetic\/molecular interventions (e.g., FGF2, p23, METTL3, lncRNA H19), novel nanodelivery systems (e.g., RosA-LIP), and selenium compounds (SeMC). This study aims to provide new insights into vascular unit injury after stroke and establish theoretical foundations and translational directions for developing neuroprotective therapies targeting ferroptosis in BMECs.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1787418","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:29:01Z","timestamp":1772083741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Insights into the potential pathogenesis and therapeutic implications of ferroptosis in brain microvascular endothelial cells during stroke"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenxiu","family":"Qin","sequence":"first","affiliation":[{"name":"Acupuncture Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, 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