Electroacupuncture Alleviates Post-stroke Cognitive Impairment Through Inhibiting miR-135a-5p/mTOR/NLRP3 Axis-mediated Autophagy

Abstract

Post-stroke cognitive impairment is a significant challenge with limited treatment options. Electroacupuncture (EA) has shown promise in improving cognitive function after stroke. Our study explores the underlying mechanism of EA in alleviating cognitive impairment through the inhibition of autophagy. We utilized a rat model of stroke induced by middle cerebral artery occlusion (MCAO) to evaluate the efficacy of EA. Treatment with EA was observed to markedly improve cognitive function and reduce inflammation in MCAO rats, as evidenced by decreased neurological deficit scores, shorter latencies in the water maze test, and diminished infarct volumes. EA also attenuated tissue damage in the hippocampus and lowered the levels of pro-inflammatory cytokines and oxidative stress markers. Although autophagy was upregulated in MCAO rats, EA treatment suppressed this process, indicated by a reduction in autophagosome formation and alteration of autophagy-related protein expression. The protective effects of EA were reversed by the autophagy activator rapamycin. EA treatment elevated the levels of microRNA (miR)-135a-5p expression, and suppression of this elevation attenuated the remedial efficacy of EA in addressing cognitive impairment and inflammation. MiR-135a-5p targeted mammalian target of rapamycin (mTOR)/NOD-like receptor protein 3 (NLRP3) signaling to repress autophagy. EA treatment inhibits autophagy and alleviates cognitive impairment in post-stroke rats. It exerts its beneficial effects by upregulating miR-135a-5p and targeting the mTOR/NLRP3 axis.