Treadmill exercise with robotic resistance improves stepping and enhances synaptic plasticity in spinal cord injured rats

Abstract

It has been shown that robotic‐assisted treadmill training with body weight support improves the recovery of stepping patterns after a spinal cord injury (SCI). We examined the effects of robotic‐applied resistive forces in a rodent model of SCI. Thirty‐three female Sprague Dawley rats received a severe mid‐thoracic spinal cord contusion injury. A baseline test was performed two weeks later, after which treadmill training using a robotic device to apply viscous forces that opposed horizontal or vertical movements of the hind limbs. One group rats (n=10) was trained with a robotic horizontal force (HF) and another group (n=7) was trained with a vertical force (VF), another group Trained (T) without force (n=8) and one group was untrained (UT) (n=8). Training was performed for 15 minutes/day, 5 days/week. After 6 weeks of training with robotic resistive forces, improvements in step cycle kinematics were observed based on data collected by the robotic device. Specifically, training with the HF significantly increased step length and forward displacement by 24% and 16% respectively relative to untrained controls. Training with VF did not affect step length parameters but instead impacted vertical velocity. Specifically, training with VF significantly increased peak vertical velocity during lift and peak vertical velocity prior to paw contact by 49% and 40% respectively. These findings suggested that treadmill training with HF and VF was effective in shaping hind limb movements in SCI rats. We next performed immunohistochemical analyses of biochemical markers for synaptic plasticity in the ventral horn of the lumbar spinal cord. The expression of synaptophysin was significantly greater after HF training compared to VF and T training (p<0.05). This finding suggested that HF training increased synapses in the lumbar spinal cord more so than other forms of training. Interestingly, a high level of synaptophysin expression was also observed in UT rats and was similar to the expression associated with HF training. On‐going experiments with VGLUT and GLYT2 labeling around motor neurons will provide greater insight into the nature of these synapses. These findings have implications for the use of treadmill exercise therapies following SCI.Support or Funding InformationNIH grant R15NS082711 to R. de Leon