Treadmill training promotes axon regeneration in injured peripheral nerves

Abstract

Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves of thy-1-YFP-H mice, in which a subset of axons in peripheral nerves express yellow fluorescent protein (YFP), were cut and repaired with allografts from non-fluorescent littermates, and then harvested two weeks later. Mice were divided into groups of low-intensity continuous training (CT, 60 minutes), low-intensity interval training (IT; one group, 10 reps, 20 minutes total), and high-intensity IT (three groups, 2, 4, and 10 reps). One repetition consisted of two minutes of running and five minutes of rest. Sixty minutes of CT resulted in the highest exercise volume, whereas two reps of IT resulted in the lowest volume of exercise. The lengths of regenerating YFP + axons were measured in images of longitudinal optical sections of nerves. Axon profiles were significantly longer than control in all exercise groups except the low-intensity IT group. In the CT group and the high-intensity IT groups that trained with four or 10 repetitions axons were more than twice as long as unexercised controls. The number of intervals did not impact axon elongation. Axon sprouting was enhanced in IT groups but not the CT group. Thus exercise, even in very small quantities, increases axon elongation in injured peripheral nerves whereas continuous exercise resulting in higher volume (total steps) may have no net impact on axon sprouting.

Effect of locomotor training on muscle performance in the context of nerve–muscle communication dysfunction

“…With regard to LT, our results show that it did not have a beneficial effect on soleus and TA muscle performance after NT. Therefore, our findings suggest that the possible increased nerve regeneration induced by LT or electrostimulation observed by histological analysis 4,8,9 has no major impact on muscle weakness and functional innervation. Discrepancies between nerve histology, motor function, and electrophysiology measures have been reported to occur during muscle reinnervation.…”

“…Increased neuromuscular activity via physical exercise, such as locomotor training (LT) and electrostimulation, have been shown to improve nerve regeneration and muscle reinnervation, as assessed using histological measures [4][5][6][7][8][9] and analysis of coordinated and complex motor functions, namely toe-spreading reflex and locomotion. 6,10 Together these earlier studies suggested that increased neuromuscular activity may improve the full recovery of muscle performance after nerve injury, such as maximal force production.…”

“…Our first hypothesis was that LT would improve muscle performance after nerve injuries that allow muscle reinnervation (nerve transection alone or crush), because muscle inactivity reduces contractility 15,16 and increased neuromuscular activity improves or accelerates nerve regeneration and muscle reinnervation. [4][5][6][7][8][9][10] Second, we examined whether LT would improve the performance of the permanently denervated soleus muscle (nerve transection with excision), as it was recently demonstrated that mechanical signals coming from passive stretch could reduce atrophy of denervated muscle 17 and thus, possibly, the deficit in maximal force production. Moreover, we studied the effect of LT on soleus muscle contractility of mice that exhibit permanent disturbed neuromuscular junction functioning due to AChE deficiency at the neuromuscular junction.…”

Efeito da associação da laserterapia com a natação no reparo morfológico do nervo isquiático e na recuperação funcional de ratos submetidos à axonotmese

“…Several experiments involving denervated animals 18 have described exercise as the factor that provides the most budding and extension of the axons, 12 the greatest increase in the number of myelinated fibers 13,14 and the best improvement in functional recovery for the injured member 15 . The results from this study are similar to those found in the literature regarding evaluating functional recovery, due to the fact that the groups that performed exercise showed better results compared to groups who did not go through the swimming protocol.…”

“…Several authors have shown beneficial results by using exercise, namely through greater budding and extension of the axons 12 , increased number of myelinated nerve fibers, 13,14 and improved functional recovery of the injured member [15][16][17] . There have been extensive discussions in the scientific community 18 regarding recommendations as per the type of exercise as well as its duration and intensity.…”