Neuropsychiatric Disease and Treatment (Aug 2021)
Electroacupuncture Pretreatment Ameliorates Anesthesia and Surgery-Induced Cognitive Dysfunction via Activation of an α7-nAChR Signal in Aged Rats
Abstract
Zhigang Wang,1,2 Tianlin Liu,1 Chunping Yin,1 Yanan Li,1 Fang Gao,1 Lili Yu,1 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, People’s Republic of China; 2Department of Anesthesiology, Handan Central Hospital, Handan, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang Tel +86 311 8860 2072Email [email protected]: Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α 7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism.Methods: Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 μg/kg), a selective antagonist of α 7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1β, were detected by Nissl staining, immunofluorescence, and Western blot assays.Results: EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1β 35 days after AS, while α-BGT partially reversed these changes.Conclusion: EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1–NF-κB via an α 7-nAChR signal in the microglia.Keywords: electroacupuncture, EA, postoperative cognitive dysfunction, POCD, α 7-nicotinic acetylcholine receptor, α 7-nAChR, microglia, high mobility group box 1, HMGB1