To investigate the role of pyroptosis in cerebral infarction and ischemia-reperfusion injury.

Twenty-four rats were randomly divided into three groups: sham-operation (Sham group, n=8), cerebral infarction (CI group, n=8), and cerebral ischemia-reperfusion (CI/R group, n=8). A focal cerebral ischemia and ischemia-reperfusion animal model was induced by the middle cerebral artery occlusion (MCAO) method. In the CI/R group, the filament was removed after 2 hours of ischemia to restore blood flow, whereas the filament was left in place in the CI group. Sham group only had surgery without inserting filament. Rats were sacrificed 24 hours post-surgery, and brain tissue and serum were collected for analysis. Pathological changes in brain tissue were observed using 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining. Western blot and immunohistochemistry were used to detect the expression of the pyroptosis-related protein Gasdermin D (GSDMD). Serum levels of interleukin (IL)-1β, S100, and neuron-specific enolase (NSE) were measured by enzyme-linked immunosorbent assay. Differences between groups were analyzed using one-way ANOVA, followed by LSD-t test for pairwise comparisons.

Compared with the Sham group, the CI group showed significantly reduced neurological function scores, extensive cerebral infarction, marked cellular edema in the infarct area, and numerous vacuoles. Compared to the CI group, the CI/R group exhibited improved neurological scores, worse infarct volume, alleviated cellular edema, and fewer vacuoles. GSDMD protein expression in the CI group [(77.07±4.18)%] was significantly higher than in the Sham group [(38.00±1.01)%], while the CI/R group [(49.33±3.42)%] showed reduced expression compared to the CI group (t=15.735, P<0.001; t=8.901, P<0.001). Serum levels of IL-1β, S100, and NSE in the Sham, CI, and CI/R groups were as follows: IL-1β [(2.69±0.83) pg/mL vs (11.63±0.93) pg/mL vs (7.42±1.06) pg/mL], S100 [(0.02±0.01) ng/mL vs (0.54±0.09) ng/mL vs (0.26±0.07) ng/mL], and NSE [(11.25±1.47) ng/mL vs (26.19±0.98) ng/mL vs (19.14±1.68) ng/mL]. The CI group had higher levels of IL-1β, S100, and NSE than the Sham group, while the CI/R group showed lower levels than the CI group, with statistically significant differences (t=6.193-18.330, all P<0.001).

Pyroptosis is involved in cerebral infarction and ischemia-reperfusion injury. Early recanalization of occluded blood vessels and restoration of cerebral blood flow can effectively inhibit pyroptosis, thereby alleviating brain damage.