Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (3): 594-600.doi: 10.4103/1673-5374.320992

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The mechanisms through which auricular vagus nerve stimulation protects against cerebral ischemia/reperfusion injury

Jing-Jun Zhao1, 2, 3, Zheng-Hui Wang4, Ying-Jie Zhang5, Wen-Jing Wang1, 2, Ai-Fang Cheng5, Pei-Jing Rong6, Chun-Lei Shan1, 2, 3, *#br#   

  1. 1Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China; 4Center of Rehabilitation Medicine, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China; 5Shanghai Research Institute of Acupuncture and Meridian, Shanghai, China; 6Institute of Acupuncture and Moxibustion, Chinese Academy of Chinese Medical Sciences, Beijing, China
  • Online:2022-03-15 Published:2021-10-15
  • Contact: Chun-Lei Shan, PhD, MD, shanclhappy@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81704163 (to JJZ), 81874035 (to CLS); the National Key R&D Program of China, No. 2018YFC2001600 (to CLS); the Shanghai Health Commission Accelerated the Development of Traditional Chinese Medicine Three-Year Action Plan Project of China, No. ZY(2018-2020)-CCCX-2001-06/2004-05 (to CLS); and the Program of Shanghai Academic Research Leader of China, No. 19XD1403600 (to CLS).

Abstract: Previous studies have shown that vagus nerve stimulation can improve patients’ locomotor function. The stimulation of the auricular vagus nerve, which is the only superficial branch of the vagus nerve, may have similar effects to vagus nerve stimulation. However, the precise mechanisms remain poorly understood. In this study, rat models of cerebral ischemia/reperfusion injury were established by modified Longa ligation. Twenty-four hours later, 7-day auricular vagus nerve stimulation was performed. The results showed that auricular vagus nerve stimulation promoted the secretion of acetylcholine, inhibited the secretion of interleukin-1β, interleukin-6, and tumor necrosis factor-α, and reduced connexin 43 phosphorylation in the ischemic penumbra and motor cortex, promoting locomotor function recovery in rats with cerebral ischemia/reperfusion injury. These findings suggested that auricular vagus nerve stimulation promotes the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury by altering the secretion of acetylcholine and inflammatory factors and the phosphorylation of connexin 43. This study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine on November 8, 2019 (approval No. PZSHUTCM191108014).

Key words: auricular vagus nerve stimulation, connexin 43, gap junction, inflammatory factor, ischemia/reperfusion injury, neurological function, neuroprotection, stroke

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