Wheel running following spinal cord injury improves locomotor recovery and stimulates serotonergic fiber growth

Abstract

Exercise, through manual step training, robotic step training or voluntary wheel running, is emerging as a promising therapy after spinal cord injury (SCI). Animal models provide a tool to investigate the mechanisms by which physical activity influences recovery from SCI. In the present study, we extend previous experiments showing improved recovery after SCI with both pre- and post-injury running in a flat-surface running wheel and investigate mechanisms of recovery. We tested a clinically relevant model using post-injury wheel running, in which we provided mice with access to wheels either 3 days or 7 days/week. Open field behavior, observed for 15 weeks following moderate T9 contusion injury, showed a significant linear increase in locomotor improvements across groups, sedentary, 3-day runners and 7-day runners. Kinematic analysis of treadmill walking revealed that both wheel-running groups, 3 and 7 days/week, improved stepping ability compared with sedentary controls. Stereological quantification of neuron number in the injured segment of the spinal cord revealed no differences between the groups. However, stereological quantification of serotonin immunostaining using isotropic virtual planes showed increases in serotonin fiber length caudal to the lesion in the running groups. These observations suggest that improvement in function may be related to changes in serotonin fibers immediately caudal to the injury epicenter.