Electroacupuncture Stimulation of the Head Motor Area Alleviates Brain Cell Pyroptosis and Neurobehaviors in Stroke Rats Through the NF-κB/NLRP3 Signaling Axis

Electroacupuncture (EA), a combination of acupuncture and electrical stimulation, is an efficient therapy for stroke. The paper intends to investigate the impact of EA stimulation of the head motor area on the neurological function of stroke rats and the underlying mechanism. An MCAO rat model was developed and intervened with EA, the NLRP3 Activator Nigericin, and the NF-κB Activator PMA. Motor function, coordination ability, neurological dysfunction, infarct volume, histopathological changes, and cortical nerve cell alterations were assessed using the Basso Beattie Bresnahan score, balance beam test, neurobehavioral score, and TTC, H&E, and Nissl stainings. Neuroinflammation degree, inflammatory cytokine levels, and cortical expression of NF-κB, NLRP3, Cleaved Caspase-1, and GSDMD-N were assessed using immunohistochemistry, immunofluorescence, ELISA, and western blot. MCAO rats treated with EA showed improved motor function and neurobehaviors. EA inhibited NF-κB/NLRP3-mediated brain cell Pyroptosis and neuroinflammation, demonstrated by decreased cortical NF-κB expression and phosphorylation, NLRP3, Cleaved Caspase-1/Pro-Caspase-1 and GSDMD-N/GSDMD expression, and GSDMD-N-positive cell count, reduction of activated microglia (Iba-1+ and Iba-1+CD68+) and astrocytes (GFAP+), decreased IL-1β and IL-18, IL-6, and tumor necrosis factor-α levels, and increased IL-10 and transforming growth factor-β levels. These findings suggest that EA may improve motor function and neurobehaviors in MCAO rats by inhibiting the NF-κB/NLRP3 pathway. Conversely, activation of the NF-κB/NLRP3 pathway attenuated the ameliorative effects of EA. EA stimulation of the head motor area mitigated brain cortical Pyroptosis and neuroinflammation via NF-κB/NLRP3 pathway suppression, thereby ameliorating motor function and neurobehaviors in MCAO rats.