Experimental neurology · 2025
The phenotypic transformation of astrocytes after AIS can be regulated by microglial GSDMD-mediated pyroptosis.
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Zhang Yige, Zhou Yifang, Zhang Wan, Qian Yiwei, Chen Zixin, Pei Lulu, Zhang Ding, Cheng Wanxuan, Tian Mengke, Zong Ce, Wang Xin, Wang Yamin, Wang Jiaxin, Ning MingMing, Tan Jun, Xia Zongping, Xu Yuming, Cao Yuan, Song Bo
Аннотация
BACKGROUND: Microglial pyroptosis contributes to the pathogenesis of ischemic stroke through multiple pathways. However, it is unclear how it contributes to the phenotype switching of neuroinflammatory/ neuroprotective astrocytes.
METHODS: This study established a mouse MCAO model and utilized microglial Gsdmd gene knockout mice to examine neuroinflammatory/neuroprotective astrocyte-related protein expression, infarct volume, mNSS scores, and other metrics. Additionally, a transwell co-culture model of microglia and astrocytes was constructed, followed by treatment with IL-1β, pyroptosis inhibitor DSF, and IL-1R1 inhibitor IL-1RA.
RESULTS: The findings confirm that microglial GSDMD protein-mediated pyroptosis influences the phenotypic transformation of neuroinflammatory/neuroprotective astrocytes. Specifically, GSDMD-mediated pyroptosis in microglia releases IL-1β, which binds to the IL-1R1 receptor, reversing neuroinflammatory / neuroprotective astrocyte polarization.
CONCLUSION: This mechanism improves AIS prognosis and may serve as a promising therapeutic candidate in AIS.
METHODS: This study established a mouse MCAO model and utilized microglial Gsdmd gene knockout mice to examine neuroinflammatory/neuroprotective astrocyte-related protein expression, infarct volume, mNSS scores, and other metrics. Additionally, a transwell co-culture model of microglia and astrocytes was constructed, followed by treatment with IL-1β, pyroptosis inhibitor DSF, and IL-1R1 inhibitor IL-1RA.
RESULTS: The findings confirm that microglial GSDMD protein-mediated pyroptosis influences the phenotypic transformation of neuroinflammatory/neuroprotective astrocytes. Specifically, GSDMD-mediated pyroptosis in microglia releases IL-1β, which binds to the IL-1R1 receptor, reversing neuroinflammatory / neuroprotective astrocyte polarization.
CONCLUSION: This mechanism improves AIS prognosis and may serve as a promising therapeutic candidate in AIS.