Electroacupuncture Ameliorates Tibial Fracture-Induced Cognitive Dysfunction by Elevating α7nAChR Expression and Suppressing Mast Cell Degranulation in the Hippocampus of Rats.

Abstract

Intracerebral neuroinflammation, closely related to brain mast cell (MC) activation, performs an integral function in the pathogenic process of postoperative cognitive dysfunction (POCD). In addition to regulating cognitive activities, the alpha-7-nicotinic acetylcholine receptor (α7nAChR) engages in the progression of cognitive deficiency. In this research, we aimed to investigate how electroacupuncture (EA) affects the cognitive function in rats after tibial fracture surgery to determine whether the underlying mechanism involves the inhibition of hippocampal MC degranulation via α7nAChR. A rat model of tibial fracture surgery for inducing POCD was developed and subjected to treatment with EA or the α7nAChR antagonist α-bungarotoxin (α-BGT) and the α7nAChR agonist PHA-543613. The spatial memory tasks in the Morris Water Maze (MWM) test showed that both EA and PHA-543613-treated rats performed significantly better than untreated rats, with reduced escape latency and increased frequency of passage through the platform. However, EA and PHA-543613 intervention decreased the protein and mRNA levels of High-mobility group box-1(HMGB-1) and proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in the serum and hippocampus, respectively, by upregulating α7nAChR in the hippocampus. Furthermore, EA and PHA-543613 pretreatment reduced the number of activated MCs and suppressed neuronal apoptosis after tibial fracture surgery in the hippocampal CA1 regions, which was reversed by α-BGT. The findings indicated that EA pretreatment ameliorated POCD after tibial fracture surgery in rats by inhibiting brain MC activation and neuroinflammation mediated by the α7nAChR-dependent cholinergic anti-inflammatory system.