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REVIEW article

Front. Immunol.

Sec. Multiple Sclerosis and Neuroimmunology

Insights into the Potential Pathogenesis and Therapeutic Implications of Ferroptosis in Brain Microvascular Endothelial Cells During Stroke

Provisionally accepted
Qin WenxiuQin Wenxiu1Yiran ZhaoYiran Zhao1Jianqiang DuJianqiang Du2Qiaoli ZhangQiaoli Zhang3Gang WeiGang Wei1Shaokang WangShaokang Wang1Ziru YuZiru Yu1Junfeng XuJunfeng Xu1Jian YangJian Yang1*Ying GaoYing Gao1*
  • 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
  • 2Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • 3Gansu University of Chinese Medicine, Lanzhou, China

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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—a novel iron-dependent lipid peroxidation-driven cell death pathway—has 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—including Meg3/p53/GPX4, TEAD1/MMP3, SESN2/System Xc−/GPX4, and SP1/TNFSF9/SLC3A2—in 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.

Keywords: Blood-Brain Barrier, brain microvascular endothelial cells, ferroptosis, mechanisms, Stroke

Received: 14 Jan 2026; Accepted: 09 Feb 2026.

Copyright: © 2026 Wenxiu, Zhao, Du, Zhang, Wei, Wang, Yu, Xu, Yang and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jian Yang
Ying Gao

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material