Forced Exercise as a Rehabilitation Strategy after Unilateral Cervical Spinal Cord Contusion Injury

Abstract

Evaluation of locomotor training after spinal cord injury (SCI) has primarily focused on hind limb recovery, with evidence of functional and molecular changes in response to exercise. Since trauma at a cervical (C) level is common in human SCI, we used a unilateral C4 contusion injury model in rats to determine whether forced exercise (Ex) would affect spinal cord biochemistry, anatomy, and recovery of fore and hind limb function. SCI was created with the Infinite Horizon spinal cord impactor device at C4 with a force of 200 Kdyne and a mean displacement of 1600-1800 microm in adult female Sprague-Dawley rats that had been acclimated to a motorized exercise wheel apparatus. Five days post-operatively, the treated group began Ex on the wheel for 20 min per day, 5 days per week for 8 weeks. Wheel speed was increased daily according to the abilities of each animal up to 14 m/min. Control rats were handled daily but were not exposed to Ex. In one set of animals experiencing 5 days of Ex, there was a moderate increase in brain-derived neurotrophic factor (BDNF) and heat shock protein-27 (HSP-27) levels in the lesion epicenter and surrounding tissue. Long-term (8 weeks) survival groups were exposed to weekly behavioral tests to assess qualitative aspects of fore limb and hind limb locomotion (fore limb scale, FLS and BBB [Basso, Beattie, and Bresnahan locomotor rating scale]), as well as sensorimotor (grid) and motor (grip) skills. Biweekly assessment of performance during wheel walking examined gross and fine motor skills. The FLS indicated a significant benefit of Ex during weeks 2-4. The BBB test showed no change with Ex at the end of the 8-week period, however hind limb grid performance was improved during weeks 2-4. Lesion size was not affected by Ex, but the presence of phagocytic and reactive glial cells was reduced with Ex as an intervention. These results suggest that Ex alone can influence the evolution of the injury and transiently improve fore and hind limb function during weeks 2-4 following a cervical SCI.