Electrical Stimulation Promotes Motoneuron Regeneration without Increasing Its Speed or Conditioning the Neuron

TLDR

Motoneurons reinnervate the distal stump after peripheral nerve transection at variable rates, with substantial reinnervation occurring within 3 weeks in the rat femoral nerve model but not completing until 10 weeks post‑repair. The authors investigated whether 20 Hz electrical stimulation synchronizes regeneration by labeling motoneurons that crossed the repair at 4 days to 4 weeks after femoral nerve transection and suture. Stimulation increased the number of axons crossing the repair within 4–7 days but did not accelerate regeneration speed, and pre‑injury conditioning had no effect, indicating that electrical stimulation promotes the onset of motor axon regeneration without increasing its speed and suggesting a combined strategy of early stimulation followed by treatments to enhance elongation.

Abstract

Motoneurons reinnervate the distal stump at variable rates after peripheral nerve transection and suture. In the rat femoral nerve model, reinnervation is already substantial 3 weeks after repair, but is not completed for an additional 7 weeks. However, this "staggered regeneration" can be temporally compressed by application of 20 Hz electrical stimulation to the nerve for 1 hr. The present experiments explore two possible mechanisms for this stimulation effect: (1) synchronization of distal stump reinnervation and (2) enhancement of regeneration speed. The first possibility was investigated by labeling all motoneurons that have crossed the repair at intervals from 4 d to 4 weeks after rat femoral nerve transection and suture. Although many axons did not cross until 3–4 weeks after routine repair, stimulation significantly increased the number crossing at 4 and 7 d, with only a few crossing after 2 weeks. Regeneration speed was studied by radioisotope labeling of transported proteins and by anterograde labeling of regenerating axons, and was not altered by stimulation. Attempts to condition the neuron by stimulating the femoral nerve 1 week before injury were also without effect. Electrical stimulation thus promotes the onset of motor axon regeneration without increasing its speed. This finding suggests a combined approach to improving the outcome of nerve repair, beginning with stimulation to recruit all motoneurons across the repair, followed by other treatments to speed and prolong axonal elongation.