Exogenous hydrogen sulfide ameliorates memory dysfunction in post-stroke depressed mice by reducing NLRP3 inflammasome activation in astrocytes

Abstract

Cognitive decline is common in post-stroke depression (PSD) and has been reported to be associated with oxidative stress. Hydrogen sulfide (H₂S)—an antioxidant gas molecule—participates in producing the antioxidant glutathione, upregulating antioxidant signals, and maintaining mitochondrial integrity. In this study, we investigated the neuroprotective effects of sodium hydrosulfide (NaHS, an H₂S donor) on cognitive impairment after PSD. After subjecting middle cerebral artery occlusion (MCAO) mice to chronic restraint stress (CRS) for 21 days, NaHS 0.1 mmol/kg was injected intraperitoneally daily for seven consecutive days. The forced swimming test (FST) and fear conditioning test (FC) were used to evaluate depression-like behavior and cognitive function. NaHS administration significantly reversed MCAO plus CRS-induced PSD and cognitive impairment, including increased immobility time, reduced context-related freezing time, elevated astrocytic pyroptosis indicated by interleukin-18 and cleaved caspase-1 in the hippocampal CA1 and CA3, downregulated oscillations in theta, and upregulated oscillations in gamma under FC conditions. H₂S provides a new perspective for treating cognitive impairment in PSD patients.