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

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.

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

“…Following transection, axons show staggered regeneration and may take substantial time to actually cross the injury site and enter the distal nerve stump ( Brushart et al, 2002). Although delayed axonal elongation might be caused by growth inhibition originating from the distal nerve itself, growth-stimu-lating influences may overcome axons stagger.…”

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

“…Electrical stimulation of lesioned femoral nerve promotes regeneration of lower motor neurons [123,124]. Brief stimulation of lesioned femoral nerves for 1 hour leads to a rapid increase in messenger RNA (mRNA) levels of BDNF and its complementary high affinity receptor trkB in the motor neurons that peaks 2 days poststimulation with maximum sixfold and fourfold increases, respectively, in comparison to contralateral intact motor neurons [25].…”

Chitin and carbon nanotube composites as biocompatible scaffolds for neuron growth

“…Tissue engineering provides an alternative approach to study tissue regeneration by use and design of biomaterials to house cells and provide a three-dimensional structure to the growing cells. For the purpose of neurons, electrically-conducting polymers are of utmost importance as electrical stimulation has been shown to be most promising to enhance nerve regeneration [4][5][6][7][8][9] as well as for stimulation of neural stem cells [10][11][12] . Thus, fabrication of conducting bio-scaffolds is an important area of study.…”