Combination of epidural spinal cord stimulation and treadmill training with body weight support attenuates spasticity in adult rats with spinal cord transection

Abstract

Background The neural control of rhythmical hindlimb locomotion is known to be organized by a central pattern generator (CPG) in the lumbar enlargement. In the previous report, epidural spinal cord stimulation (SCS) for CPG with treadmill training facilitated restoration of locomotion in patient with motor incomplete spinal cord injury. However, the precise mechanism of improvement is still unclear. The purpose of this study was to elucidate efficacy and molecular mechanism of SCS with treadmill training. Methods Ten female Sprague-Dawley rats were used in this study. The rats were housed with food and water under a 12 h/12 h light-dark cycle. We performed spinal cord transection at the T8-T9 level. After two weeks, the rats were divided into SCS group and control group. The rats in SCS group were performed implantation of an electrode at L2 level. SCS and body weight support treadmill training were performed for 30 minutes per day, 5 days per weeks, for 4 weeks. The rats in the control group were performed treadmill training without stimulation for same period. We evaluated hind-limb locomotor function by using Basso-Beattie-Bresnahan (BBB) score. We also assessed resistance force for full extension of hindlimb as evaluation of spasticity. For histological examination, we performed immunostaining for glutamic acid decarboxylase-65 (GAD65) of lumbar enlargement after behavioral assessment. Results There was no significant difference of BBB score between two groups, but spasticity of hind-limb in SCS group was significantly reduced. Histological assessment revealed that expression of GAD65 tended to increase in the SCS group Conclusions SCS ameliorated hindlimb spasticity. It was suggested that up-regulation of GAD65 involved suppression of spasticity.