Effects of Electroacupuncture Stimulation on Motor Function Recovery in Mice After Spinal Cord Injury by Regulating...

Although it has been shown that electroacupuncture (EA) can regulate the activation of astrocytes, forming a stable microenvironment for nerve cell survival, and participating in the repair of spinal cord injury (SCI), the underlying mechanisms are not fully understood. The study aimed to investigate the effects of EA stimulation on motor function recovery in mice after SCI by regulating astrocyte activation, and explore the involvement and regulatory role of Hippo-YAP signaling pathway. In this study, we established T10 thoracic SCI model by clip compression technique, and applied EA at Jiaji points on both sides of the spine at T12 and L2 levels at 6 h after model establishment. The results showed that compared with the SCI group, the EA group showed significantly higher BMS scores at 7, 14 and 28 days post-injury, and better hindlimb motor function recovery at 28 days after SCI (P < 0.05). An improvement in the degree of inflammatory reaction, the extent of glial scar formation, and the atrophy of neurons, an increase in the number of Nissl bodies, a decrease in karyorrhexis were observed in the EA group at different time points post-injury. The EA group showed significantly decreased expression of inflammatory factors (IL-1β, TNF-a and IL-6), GFAP and CSPGs, increased expression of p-MST1 and p-YAP, decreased expression of MST1 and YAP, increased p-MST1/MST1 ratio and p-YAP/YAP ratio than the SCI group at each time point post-injury (all P < 0.05). The EA group also showed significantly up-regulated expression of ZO-1, CLN-5, 5-HT and NFH, significantly increased density of NeuN-positive neurons and significantly decreased expression of CS56, CD68 compared to the SCI group at 14 days post-injury (all P < 0.05). Our findings suggest that EA stimulation may down-regulate the activation level of the astrocytes by activating the Hippo-YAP signaling pathway and decreasing the transcriptional activity of its downstream effector YAP, thus inhibiting the formation of glial scar and the release of inflammatory factors, enhancing the repair of the blood-spinal cord barrier, facilitating neuron survival and axon regeneration, leading to improvement in the recovery of hindlimb motor function in mice after SCI.