Electroacupuncture attenuated cerebral ischemic injury and neuroinflammation through α7nAChR-mediated inhibition of NLRP3 inflammasome in stroke rats

Abstract

Background Our previous research confirmed that electroacupuncture (EA) stimulus elicits neuroprotective effects against cerebral ischemic injury through α7 nicotinic acetylcholine receptor (α7nAChR)-mediated inhibition of high-mobility group box 1 release mechanism. This study investigated whether the signal transducer of α7nAChR and inhibition of NLRP3 inflammasome are involved in the neuroprotective effects of EA stimulus. Methods In adult male Sprague-Dawley rats, the focal cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO) models for 1.5 h. The expression of NLRP3 inflammasome in the penumbral tissue following reperfusion was assessed by western blotting and immunoflourescent staining. The infarct size, neurological deficit score, TUNEL staining and the expression of proinflammatory factors or anti-inflammatory cytokines were evaluated at 72 h after reperfusion in the presence or absence of either α7nAChR antagonist (α-BGT) or agonist (PHA-543,613). Results The contents of inflammasome proteins were gradually increased after cerebral ischemia/reperfusion (I/R). EA stimulus attenuated NLRP3 inflammasome mediated inflammatory reaction and regulated the balance between proinflammatory factors and anti-inflammatory cytokines. The agonist of α7nAChR induced similar neuroprotective effects as EA stimulus. In contrast, α7nAChR antagonist reversed not only the neuroprotective effects, but also the inhibitory effects of NLRP3 inflammasome and the regulatory effects on the balance between proinflammatory factors and anti-inflammatory cytokines. Conclusions These results provided compelling evidence that α7nAChR played a pivotal role in regulating the activation and expression of NLRP3 inflammasome in neurons after cerebral I/R. These findings highlighted a novel anti-inflammatory mechanism of EA stimulus by α7nAChR modulating the inhibition of NLRP3 inflammasome, suggesting that α7nAChR-dependent cholinergic anti-inflammatory system and NLRP3 inflammasome in neurons might act as potential therapeutic targets in EA induced neuroprotection against cerebral ischemic injury.

Carthamin yellow improves cerebral ischemia‑reperfusion injury by attenuating inflammation and ferroptosis in rats

“…Hippocampal NF-κB mRNA expression, and serum TNF-α and IL-1β levels were increased in response to ischemia stroke ( 8 ). Cerebral ischemia-reperfusion injury activated the NLRP3 inflammasome proteins in rats, which could be suppressed by electroacupuncture, leading to improvement of neurological deficit scores and infarct sizes in middle cerebral artery occlusion (MCAO) model rats ( 9 ).…”

Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

“…Using the PPI-T test, we performed the first pharmacological experiments on the effects of nicotinic receptor (nAChRs) agonists α7 and α4β2 subtypes (respectively PNU-282987 (PNU) and RJR2403) on HBH, in low selective doses equal to their K i and some higher. It is known that nAChRs are involved in hypoxic or ischaemic preconditioning in the brain and other organs, and it was most convincingly demonstrated for the α7 and α4β2nAChRs [ 40 , 41 , 42 , 43 , 44 ]. In our experiments, PNU (but not RJR2403), and more pronouncedly its solvent dimethyl sulfoxide (DMSO, 2–3%), showed a PPI-associated effect on the efficiency of HBH, the direction of which changed to the opposite at the border when PPI = 36–40% [ 20 , 45 ].…”

The Therapeutic Effect of Electroacupuncture Therapy for Ischemic Stroke

“…EA at Shuigou (GV26) significantly improved the neurological deficit symptoms in rats with ischemic stroke, which may be involved in upregulating Wnt7a and LEF1 proteins and mRNAs levels and decreasing GSK-3 β and DKK1 proteins and mRNAs levels [ 37 ]. Jiang et al showed a novel anti-inflammatory mechanism induced by EA via α 7nAChR-mediated inhibition of NLRP3 inflammasome in rats after cerebral ischemic injury [ 38 ].…”