Electroacupuncture Alleviates HIF1-α-mediated Early Mitophagy in Spinal Cord Injury

The inhibitory microenvironment around spinal cord injury severely restricted functional repair after injury. Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment. Hypoxia-inducible factor1α(HIF1-α) can mediate mitochondrial autophagy in neurodegenerative diseases, but the mechanisms are complex and diverse, which need to be further elucidated. Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury, promote long-term neurological function recovery in SCI patients, but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown. Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture. In this study, a model of spinal cord injury was established in Sprague-Dawley rats using the modified Allen method. Motor recovery following spinal cord injury was evaluated by Basso Beattie Bresnahan score. Western blotting, quantitative real-time PCR, immunofluorescence, transmission electron microscopy and Nissl staining were performed to detect HIF1-α mediated mitophagy. HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury. Electroacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury, reduce cell apoptosis and injury area, promote neuronal survival. Electroacupuncture may serve as a promising strategy for spinal cord injury treatment, by alleviating HIF1-α mediated early mitochondrial autophagy.