Byline: Hui-Ling. Wang, Fei-Lai. Liu, Rui-Qing. Li, Ming-Yue. Wan, Jie-Ying. Li, Jing. Shi, Ming-Li. Wu, Jun-Hua. Chen, Wei-Juan. Sun, Hong-Xia. Feng, Wei. Zhao, Jin. Huang, Ren-Chao. Liu, Wen-Xue. Hao, Xiao-Dong. Feng
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting (GV24) and Baihui (GV20) acupoints, with a dilatational wave (1-20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3K/Akt signaling pathway-related factors Beclin-1, mammalian target of rapamycin (mTOR), and PI3K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting (GV24) and Baihui (GV20) acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China (approval No. 8150150901) on March 10, 2016.
Cognitive impairment and decline in patients with stroke during the acute and chronic phases, particularly the impairment of learning and memory, has a very high clinical incidence. Clinical studies have indicated that 25-30% of post-stroke impairment survivors suffer from immediate or delayed cognitive impairment, which markedly affects the rehabilitation programs necessary to improve physical ability and activities of daily living (Kalaria et al., 2016; Pantoni, 2017). Numerous recent studies have examined electroacupuncture (EA) treatment, which is based on acupuncture techniques from ancient China and combines traditional acupuncture with modern electrical stimulation. EA has dual therapeutic effects and represents a simple, convenient, and cost-effective treatment option that has been widely used to treat cognitive impairments following cerebral ischemia (Pollock et al., 2014; Liu et al., 2015; Han, 2019). However, the functional mechanisms that underlie the EA-mediated amelioration of post-stroke cognitive impairment have not yet been fully elucidated.
Many studies have suggested that autophagy plays an important role in the formation and development of cognitive impairment, and...