MINI REVIEW article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicNeuroinflammation: Mechanisms and Therapeutic InterventionsView all 24 articles
Targeting Glial Cell Pyroptosis and Neuroinflammation in Post-Stroke Depression: From Molecular Mechanisms to Therapeutic Strategies
Provisionally accepted
Xinyao Li1
Yuanyuan Wei1
Yuqing She1Wenjuan Long1Sitong Zhou1
Mingqin Shi1Zihui Wang1Xuelian Zou1Jianqin Mao1Xiangdian Xiao2*
Hongling Shi3*
Dongdong Qin1*- 1Yunnan University of Chinese Medicine, Kunming, China
- 2Qujing Medical College, Qujing, China
- 3The Third People’s Hospital of Yunnan Province, Kunming, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Post-stroke depression (PSD) represents a prevalent and debilitating sequela following cerebrovascular accidents, with its underlying pathophysiology intricately linked to neuroinflammatory processes. Emerging evidence implicates glial cell pyroptosis depending on Caspase-gasdermin D (Casp-GSDMD), orchestrated by the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated inflammatory cascades, as a central mechanism in PSD pathogenesis. This review provides a comprehensive analysis of the molecular mechanisms governing glial cell pyroptosis and its dual role in PSD. Specifically, ischemia and hypoxia induce mitochondrial dysfunction and reactive oxygen species (ROS) accumulation, thereby promoting the release of pro-inflammatory cytokines, including IL-1β and IL-18, via the NLRP3/Caspase-1/GSDMD axis. This subsequently exacerbates neuroinflammation and disrupts the blood-brain barrier (BBB) integrity. Furthermore, aberrant activation of pyroptosis-related molecules can trigger neuronal death and impair synaptic plasticity, directly contributing to depressive symptoms. Consequently, therapeutic interventions targeting key nodes within the pyroptosis pathway, such as NLRP3, Caspase-1/4/11, and GSDMD, hold considerable promise, encompassing small molecule inhibitors, natural compounds, and combination therapies. This review synthesizes the multifaceted mechanisms of glial cell pyroptosis in PSD, highlighting the unique therapeutic potential of targeting the pyroptosis pathway to enhance post-stroke neurorepair and mitigate emotional disturbances. These findings may facilitate the identification of novel therapeutic targets and strategies for the diagnosis and management of PSD.
Keywords: post-stroke depression, glial cell pyroptosis, Neuroinflammation, Molecular mechanisms, therapeutic strategies
Received: 31 Jul 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Li, Wei, She, Long, Zhou, Shi, Wang, Zou, Mao, Xiao, Shi and Qin. 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:
Xiangdian Xiao
Hongling Shi
Dongdong Qin
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.