Shi Lei, Qian Qiheng, Xie Jiding, Yang Taoshuo, Zhao Xinyu, Meng Xiangqi, Dai Jingang, Jin Qiguan
College of Physical Education, Yangzhou University, Yangzhou, Jiangsu, China.
Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China.
Front Immunol. 2025 Aug 22;16:1649790. doi: 10.3389/fimmu.2025.1649790. eCollection 2025.
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, small-molecule 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.
创伤性脊髓损伤（TSCI）是一种严重的神经系统疾病，治疗选择有限，且极有可能导致永久性残疾。在TSCI引发的多方面继发性损伤机制中，焦亡——一种程序性细胞死亡的炎症形式——已成为关键的病理过程。特别是，小胶质细胞焦亡在加剧神经炎症和破坏组织稳态方面起着关键作用，从而放大继发性损伤级联反应。本综述全面概述了介导小胶质细胞焦亡的分子途径，包括经典途径（NLRP3-半胱天冬酶-1-GSDMD）、非经典途径（半胱天冬酶-11-GSDMD）和非典型途径（半胱天冬酶-3/8-GSDME/GSDMC）信号传导。我们还研究了旨在抑制小胶质细胞焦亡的近期治疗策略，如基于细胞外囊泡的递送系统、小分子化合物和基因靶向方法，并评估它们在脊髓损伤后促进神经和运动恢复的潜力。通过阐明小胶质细胞焦亡的病理意义和治疗前景，本综述为其作为脊髓损伤干预靶点的转化潜力提供了新的视角。
