The phenotypic transformation of astrocytes after AIS can be regulated by microglial GSDMD-mediated pyroptosis.

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.