REVIEW article
Front. Neurol.
Sec. Stroke
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1641985
Neutrophil Extracellular Traps in Ischemic Stroke: Mechanisms, Clinical Implications, and Therapeutic Potential
Provisionally accepted
- 1First Affiliated Hospital, Guangxi Medical University, Nanning, China
- 2The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- 3Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
- 4The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
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Ischemic stroke remains a leading cause of mortality and disability, with many patients failing to benefit from reperfusion therapies due to lysis-resistant thrombus formation and severe neuroinflammation. This highlights an urgent need to target the fundamental mechanisms linking these two processes. Neutrophil extracellular traps (NETs)—web-like structures of DNA and cytotoxic proteins—have emerged as a critical mediator of stroke pathology. While essential for host defense, their dysregulated formation in the cerebral microvasculature drives a vicious cycle of tissue injury.This review synthesizes evidence demonstrating that NETs are not mere bystanders but active drivers of stroke pathology. We dissect the core mechanisms by which they mediate three primary detrimental effects: (1) promoting stable, lysis-resistant thrombi, which directly contributes to poor clinical outcomes; (2) compromising blood-brain barrier integrity; and (3) amplifying the neuroinflammatory cascade.Furthermore, we evaluate the clinical utility of NETs as powerful biomarkers for diagnosis and prognosis, and we critically analyze emerging therapeutic strategies aimed at dismantling them. While targeting NETs with agents like DNase I or PAD4 inhibitors holds immense promise, we argue that significant translational challenges—such as ensuring therapeutic specificity and defining the optimal treatment window—must be overcome. In conclusion, targeting the thrombo-inflammatory functions of NETs represents a paradigm shift from a purely fibrin-centric view of stroke, opening new avenues for developing more effective therapies.
Keywords: neutrophil extracellular traps, ischemic stroke, Neuroinflammation, biomarkers, therapeutic targets
Received: 24 Jun 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 He, Wu, Liu and Ye. 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:
Ying Liu, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
Ziming Ye, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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.