Electro-acupuncture-modulated miR-214 prevents neuronal apoptosis by targeting Bax and inhibits sodium channel Nav1.3 expression in rats after spinal cord injury

Electro-acupuncture (EA) has been proven to contribute towards neurologic and functional recoveries in spinal cord injury (SCI), but the underlying mechanism remains largely unknown especially regarding the effects of preventing neuronal apoptosis and alleviating neuropathic pain involved in the development of EA. In this study, we evaluated the effect of EA treatment in an animal model of SCI using the Basso, Beattie, and Bresnahan (BBB) score method, lesion volume by cresyl violet staining and neuronal apoptosis by TUNEL staining. Our results showed that EA therapy improved functional recovery, and reduced tissue loss and neuronal apoptosis after SCI. Meanwhile, we found that proapoptotic proteins (cleaved-caspase-3, 9 and cleaved-PARP) were downregulated and antiapoptotic protein Bcl-2 was upregulated following EA. To further explore the antiapoptotic effect of EA treatment, we verified that a large set of microRNAs (miRNAs) expression were altered following EA treatment and the miR-214 was one of the miRNAs being most significantly upregulated. Importantly, we validated both apoptosis related protein Bax and pain related protein Nav1.3 as two functional targets of miR-214 in vitro and vivo. Furthermore, our data showed that EA attenuates SCI-induced Nav1.3 and Bax upregulation in injured spinal cord via upregulating miR-214. These results suggest that miR-214 played an important role after SCI in the process of EA therapy, and the miR-214 could become an attractive novel therapeutic target for the treatment of SCI.