Exercise and Peripheral Nerve Grafts as a Strategy to Promote Regeneration after Acute or Chronic Spinal Cord Injury

Therapeutic interventions after spinal cord injury (SCI) routinely are designed to address multiple aspects of the primary and/or secondary damage that occurs. Exercise has a demonstrated efficacy for post-SCI complications such as cardiovascular dysfunction, neuropathic pain, and chronic inflammation, yet there is little understanding of the mechanisms by which improvements might result from this non-invasive approach. Here we review several of our observations of molecular and cellular changes within the injured spinal cord following acute or delayed exercise regimens that illustrate the potential for positive effects on neuroprotection and rehabilitation. Further, we provide new information about the role of exercise in promoting the regeneration of spinal axons into peripheral nerve grafts (PNGs) placed immediately or 6 weeks after injury. Acute and chronically injured propriospinal neurons within the lumbar spinal cord displayed the greatest propensity for enhanced regeneration after exercise, which correlates with the direct sensory input to this region from exercised hindlimb muscles. Future studies will extend these observations by testing whether exercise will boost the regenerative effort of axons to extend beyond the graft, interact with intraspinal targets, and establish functional connections across a lesion.