Electro-Acupuncture Inhibits p66Shc-Mediated Oxidative Stress to Facilitate Functional Recovery After Spinal Cord Injury
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Electro-Acupuncture Inhibits p66Shc-Mediated Oxidative Stress to Facilitate Functional Recovery After Spinal Cord Injury Ming Cheng 1,2 & Xiaojing Wu 1 & Fei Wang 1 & Bo Tan 1 & Jiang Hu 1 Received: 9 March 2020 / Accepted: 19 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Oxidative stress is the core problem in improving secondary spinal cord injury (SCI). To investigate the effect of electroacupuncture with different frequencies on neuroinflammation, oxidative stress injury, as well as related signaling pathways, male Sprague-Dawley (SD) rats were induced using operation for model SCI and then treated with electrical stimulation at low frequency (2 mA, 0.2 Hz), medium frequency (2 mA, 50 Hz), and high frequency (2 mA, 100 Hz), respectively. Here, we first demonstrated that the JNK/p66Shc signal pathway promoted ROS generation and inhibited the anti-oxidation effect of FoxO3a to induce oxidative stress damage after SCI and the mechanism of electro-acupuncture in anti-oxidative stress. Electro-acupuncture facilitated functional recovery after SCI and improved the apoptosis of neurons. Furthermore, p38MAPK-mediated microglia activation and inflammatory reaction and JNK/p66Shc-mediated ROS generation and oxidative stress damage were both attenuated by electro-acupuncture. However, the inhibitory effect of electro-acupuncture on p38MAPK was enslaved to the acupuncture frequency, but the ROS generation and phosphorylation of p66Shc were effectively inhibited by electro-acupuncture. Therefore, the activation of JNK/p66Shc promoted the ROS-induced oxidative stress damage after SCI, and inhibiting the phosphorylation of p66Shc-mediated oxidative stress was the key target of electro-acupuncture to facilitate functional recovery SCI, but not p38MAPK. Keywords Spinal cord injury . Electro-acupuncture . Oxidative stress . JNK/p66Shc . ROS
Introduction
Contribution of the paper: Our study contributes to reveal the mechanism of electro-acupuncture in anti-oxidant stress after spinal cord injury. * Jiang Hu [email protected] Ming Cheng [email protected] Xiaojing Wu [email protected] Fei Wang [email protected] Bo Tan [email protected] 1
Department of Orthopedics, Sichuan Academy of Medical Sciences and Sichuan People’s Hospital, Chengdu 610072, China
2
Department of Orthopedics, JinNiu District People’s Hospital of Chengdu, Chengdu 610036, China
Spinal cord injury (SCI) is a serious traumatic disease, with a two-step process involving primary injury subsequently followed by secondary injury. Primary injury usually occurs as a result of mechanical injury and acute necrosis, whereas secondary injury occurs due to oxidative stress reaction, inflammatory reaction, calcium mobilization, and a series of pathophysiological processes (Ambrozaitis et al. 2006). SCI is characterized by apoptotic or necrotic events; however, the predominant causes of such events are mediated by oxidative stress (Jia et al. 2012; Hall 1993). Therefore, reducing oxidative stress becomes the key to the trea
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