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The Journal of Neuroscience, August 1, 2002, 22(15):6631-6638

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

Thomas M. Brushart^{1, 2}, Paul N. Hoffman^{2, 3}, Richard M. Royall⁴, Beth B. Murinson², Christian Witzel¹, and Tessa Gordon⁵

Departments of ¹ Orthopaedics, ² Neurology, and ³ Opthalmology, Johns Hopkins School of Medicine, and ⁴ Department of Biostatistics and Statistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore Maryland 21287, and ⁵ Department of Pharmacology, Division of Neuroscience, University of Alberta, Alberta T6G 2S2, Canada

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.

Key words: electrical stimulation; peripheral nerve; anterograde tracing; BDNF; conditioning; neurobiotin

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22156631-08$05.00/0

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