Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery

Treadmill training with weight-support is a therapeutic strategy used in human patients after spinal cord injury (SCI). Exercise leads to locomotor improvement in a variety of animal models; however, the effect of exercise on axonal regrowth has not been directly examined. This study used several locomotor tests, including kinematic gait analysis, to analyze the differences between treadmill-trained and untrained mice in the usage of their paretic hindlimb following a low thoracic hemisection. Analysis of muscle atrophy, anterograde axonal tracing and expression of the synaptic markers synaptophysin and PSD95 were used to correlate observed behavioural changes with anatomical data. Treadmill trained mice showed significant improvement in use of their paretic hindlimb after 4 weeks of exercise compared to untrained mice in an open field locomotor test (Basso-Beattie-Bresnahan [BBB] scale), grid walking and climbing and inter-limb coordination tests. Movement of their hip joint started to approximate the pattern of intact mice, with concomitant use of their ankle. Unlike untrained mice, exercised mice showed decreased muscle atrophy, increased axonal regrowth and collateral sprouting proximal to the lesion site, with maintenance of synaptic markers on motor neurons in the ventral horn. However, there was no axonal regeneration into or across the lesion site indicating that the improved behaviour may have been, at least in part, due to enhanced neural activity above the lesion site.