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.

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies

“…Most studies on the model of POCD utilized abdominal and hepatectomy. Moreover, two studies employed tibial fracture ( Wang et al, 2021 ; Zhou et al, 2022 ), while femoral fracture ( Wang M et al, 2022 ; Wang XF et al, 2022 ) and appendectomy ( Zhu et al, 2023 ) were each used in one study. The choice of acupuncture points for EA included GV20, LI4, GV14, PC6, ST36, GV24, GB13, LI11, and the frontoparietal suture.…”

“…Additional assessment criteria included the Y-maze Test and Puzzle Box Test ( Ho et al, 2022 ). Sample selection in all studies was primarily the hippocampus, though several studies also included blood and feces ( Liu et al, 2019 ; Ho et al, 2022 ; Wang M et al, 2022 ; Wang XF et al, 2022 ; Zhou et al, 2022 ; Zhu et al, 2023 ). The hypothalamus ( Chen L et al, 2019 ; Chen Y et al, 2019 ) and frontal cortex ( Ho et al, 2022 ) were each investigated in one study.…”

“…During stress, disease, or trauma, MCs can become overly activated, impacting the blood–brain barrier, neurons, and glial cells ( Skaper et al, 2017 ). In a model of POCD induced by tibial fracture surgery, EA pre-treatment at the GV20 point inhibited MC degranulation associated with hippocampal α7nAChR activation, downregulated the expression levels of IL-1β, HMGB-1, and TNF-α in serum and the hippocampus, thereby improving cognitive deficits in rats ( Zhou et al, 2022 ).…”

Electroacupuncture improves postoperative cognitive dysfunction by inhibiting ferroptosis via TFR1-DMT1-FPN pathway

“…[17] In addition to anesthesia, tibial fracture surgery is a major procedure that can have a signi cant impact on cognitive function and increase the risk of postoperative cognitive dysfunction. [18][19][20][21] Currently, there is no fully effective treatment for postoperative cognitive dysfunction. Therefore, it is crucial to identify the role of ferroptosis in the development of postoperative cognitive dysfunction, elucidate the underlying mechanisms, and identify potential therapeutic targets.…”