Wireless Epidural Electrical Stimulation in Combination With Serotonin Agonists Improves Intraspinal Metabolism in Spinal Cord Injury Rats

Abstract

Objectives: The combination of epidural electrical stimulation (EES) and serotonin agonists (5-HTA) effectively restores rhythmic lower-limb movements and improves intraspinal hemodynamics after spinal cord injury (SCI). Nonetheless, whether EES + 5-HTA improves intraspinal metabolism remains unclear. The present study aimed to evaluate the effects of EES + 5-HTA on intraspinal metabolism in SCI rats. Materials and Methods: Wireless EES (WEES) implantation with complete T8 transection was performed in SCI rats. Electrodes were placed at the T12 and L2 vertebral levels. After rest for a week, the SCI rats received 11 weeks of WEES + 5-HTA treatment and treadmill training. WEES was switched off after each daily training. Locomotor function was evaluated by motion capture at week 12. Positron emission tomography–computed tomography was conducted to evaluate basal metabolism when WEES was switched off and assess task metabolism when WEES was switched on. Results: With locomotor recovery after training for 11 weeks, WEES + 5-HTA conjointly improved basal metabolism (vs. each intervention alone; p < 0.05) and linearly modulated task metabolism in a frequency-dependent manner (R2 = 0.8901). Furthermore, 60 Hz of WEES was identified as the threshold for the extensive activation of the spinal cord's task metabolism below the transection plane (p < 0.05). Conclusions: WEES + 5-HTA could conjointly restore basal metabolism to a healthy level and modulate task metabolism by adjusting the stimulation frequency.