Electroacupuncture ameliorates motor dysfunction via inhibiting p66Shc-mediated oxidative stress and endoplasmic reticulum stress in rats with spinal cord injury
Background: Spinal cord injury (SCI) is a severe neurological disorder for which there is currently no effective treatment. Electroacupuncture (EA) is a means of combining traditional acupuncture 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 treatment on the repair of SCI and to investigate the possible mechanisms. Methods: Rats were randomly divided into sham, sham+EA, SCI and SCI+EA
... EA, SCI and SCI+EA four groups after SCI model was established. Rat motor function was assessed by the Basso, Beattie and Bresnahan locomotor rating scale, inclined plane test and footprint analysis. Histological alterations 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), as well as 4-hydroxynonenal (4-HNE) levels. The expression of p66Shc and endoplasmic reticulum stress (ERS) were detected to explore the involved mechanisms.Results: EA treatment significantly improved motor functional recovery, reduced spinal cord lesion cavity and neuronal chromatolysis after SCI. Meanwhile, EA treatment 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 treatment also attenuated 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-mediated oxidative stress and ERS in rats.