MINI REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1649790
Microglial Pyroptosis as a Therapeutic Target After Traumatic Spinal Cord Injury: Current Progress and Future Directions
Provisionally accepted
- 1Yangzhou University, Yangzhou, China
- 2Suzhou Hospital of Traditional Chinese Medicine, Suzhou, China
- 3China Academy of Chinese Medical Sciences, Beijing, China
- 4University of Glasgow, Glasgow, United Kingdom
- 5Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, China
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Traumatic spinal cord injury (TSCI) is a devastating neurological condition with limited therapeutic options and a high likelihood of permanent disability. Among the multifaceted secondary injury mechanisms triggered by TSCI, pyroptosis-an inflammatory form of programmed cell death-has emerged as a key pathological process. In particular, microglial pyroptosis plays a pivotal role in exacerbating neuroinflammation and disrupting tissue homeostasis, thereby amplifying the secondary injury cascade. This review provides a comprehensive overview of the molecular pathways mediating microglial pyroptosis, including canonical (NLRP3-caspase-1-GSDMD), non-canonical (caspase-11-GSDMD), and atypical (caspase-3/8-GSDME/GSDMC) signaling. We also examine recent therapeutic strategies aimed at suppressing microglial pyroptosis-such as extracellular vesicle-based delivery systems, smallmolecule compounds, and gene-targeted approaches-and assess their potential to enhance neurological and motor recovery following SCI. By elucidating both the pathological significance and therapeutic promise of microglial pyroptosis, this review offers novel perspectives on its translational potential as a target for spinal cord injury intervention.
Keywords: Traumatic spinal cord injury, pyroptosis, Microglia, Inflammation, NLRP3, GSDMD
Received: 20 Jun 2025; Accepted: 05 Aug 2025.
Copyright: © 2025 Shi, Qian, Xie, Yang, Zhao, Meng, Dai and Jin. 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:
Xiangqi Meng, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, China
Jingang Dai, China Academy of Chinese Medical Sciences, Beijing, China
Qiguan Jin, Yangzhou University, Yangzhou, 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.