Electroacupuncture Ameliorates Motor Dysfunction via Inhibiting p66Shc-Associated Oxidative Stress and Endoplasmic Reticulum Stress in Rats with Spinal Cord Injury

Abstract Background: Spinal cord injury (SCI) is a severe neurological disorder for which there is currently no effective treatment. Electroacupuncture (EA) is a type of traditional acupuncture combined with modern electrotherapy, which has been widely used and verified to have neuroprotective effects. The aim of this study was to evaluate the effects of EA stimulation on the repair of SCI and to investigate the possible mechanisms. Methods: Sprague-Dawley rats were randomly divided into sham, sham+EA, SCI and SCI+EA four groups. Rat motor function was assessed by the Basso, Beattie and Bresnahan locomotor rating scale, inclined plane test and footprint analysis. Histological alterations of spinal cords were examined with hematoxylin-eosin and Nissl staining. Oxidative stress was evaluated by measuring reactive oxygen species (ROS), glutathione (GSH), total antioxidant capacity (T-AOC), 3-nitrotyrosine (3-NT), and 4-hydroxynonenal (4-HNE) levels. The changes in p66Shc expression and endoplasmic reticulum stress (ERS) were detected to explore the involved mechanisms.Results: EA stimulation significantly improved rat motor functional recovery, reduced spinal cord lesion cavity and neuronal chromatolysis after SCI. Concomitantly, EA stimulation alleviated oxidative stress, as indicated by suppression of ROS production, increase in GSH and T-AOC levels and reduction of 3-NT and 4-HNE expression. Further, EA stimulation markedly eliminated the aberrant increase of p66Shc due to SCI in rats. More notably, EA stimulation was also able to attenuate ERS via down-regulation of glucose-regulated protein 78, activating transcription factor 4, C/EBP homologous protein, X-box binding protein 1 and activating transcription factor 6 expression in rat spinal cord tissues after SCI. Conclusions: These findings suggest that EA is a potential strategy for treatment of SCI, and the mechanism might be, at least in part, associated with mitigation of p66Shc-associated oxidative stress and ERS in rats.