Electroacupuncture ameliorates learning and memory impairment by inhibiting inflammation and promoting synaptic plasticity via inhibition of the NF-KB/NLRP3 signaling pathway in cerebral ischemic rats.

Abstract

OBJECTIVE: Electroacupuncture (EA) has a protective effect on cerebral ischemic injury. However, the specific mechanism of action of EA has not been studied. In this study, we investigated whether EA was involved in the treatment of learning and memory impairment in rats with cerebral ischemia‒reperfusion injury (CIRI) through the NF-KB/NLRP3 signaling pathway. METHODS: Ninety-five male Sprague-Dawley (SD) rats were randomly divided into five groups, each consisting of 19 rats. A rat model of cerebral ischemia was established using transient middle cerebral artery occlusion (tMCAO) combined with cerebral blood flow monitoring. Intervention treatments consisted of electroacupuncture and lipopolysaccharide (an NF-κB agonist) injection. The behavior, spatial learning, and memory ability of the rats were evaluated with the Morris water maze method. The degree of brain injury in the rats was observed via triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (H&E), and Fluoro-Jade B (FJB) staining. The expression levels of proteins related to the inflammatory response, pyroptosis, and synaptic plasticity were determined via western blotting and immunofluorescence staining. Changes in dendrites and spines were observed via Golgi-Cox staining. RESULTS: Compared with those of the tMCAO group, the neural function scores and escape latency of the EA+tMCAO group were reduced. The cerebral infarct volume and the number of denatured neurons decreased. NF-κB, caspase-1, NLRP3, and IL-18 expression levels were significantly decreased. PSD95, SYP, and BDNF expression levels were significantly increased. The total number of dendrite junctions and the total length of dendrites increased. Compared with the EA+tMCAO and NS+EA+tMCAO groups, the escape latency in the lipopolysaccharide (LPS)+EA+tMCAO group was significantly increased. NF-κB, IL-18, and cleaved caspase-1 expression levels were elevated. CONCLUSION: EA may inhibit NF-κB/NLRP3 pathway proteins; regulate the neuroinflammatory response; promote the expression of PSD-95, SYN, and BDNF; improve the structure of dendrites and dendritic spines; and alleviate cognitive impairment in rats with CIRI.