Taken together, our findings suggest that intervention in the GSDMD/Drp1 pathway, specifically using NSA or Mdivi-1, may partially alleviate neuroinflammation, mitigate mitochondrial changes, attenuate neuronal and synaptic damage, rectify abnormalities in neural oscillations, and ultimately ameliorate cognitive deficits in a murine model of SAE. Here, GSDMD is linked to Cognitive impairment.