Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration

Functional recovery is often poor despite the capacity for axonal regenerat ion in the peripheral nervous system and advances in microsurgical techniqu e. Regeneration of axons in mixed nerve into inappropriate pathways is a ma jor contributing factor to this failure. In this study, we use the rat femo ral nerve model of transection and surgical repair to evaluate (1) the effe ct of nerve transection on the speed of regeneration and the generation of motor-sensory specificity, (2) the efficacy of electrical stimulation in ac celerating axonal regeneration and promoting the reinnervation of appropria te muscle pathways by femoral motor nerves, and (3) the mechanism of action of electrical stimulation. Using the retrograde neurotracers fluorogold an d fluororuby to backlabel motoneurons that regenerate axons into muscle and cutaneous pathways, we found the following. (1) There is a very protracted period (10 weeks) of axonal outgrowth that adds substantially to the delay in axonal regeneration (staggered regeneration). This process of staggered regeneration is associated with preferential motor reinnervation (PMR). (2 ) One hour to 2 weeks of 20 Hz continuous electrical stimulation of the par ent axons proximal to the repair site dramatically reduces this period (to 3 weeks) and accelerates PMR. (3) The positive effect of short-term electri cal stimulation is mediated via the cell body, implicating an enhanced grow th program. The effectiveness of such a short-period low-frequency electric al stimulation suggests a new therapeutic approach to accelerate nerve rege neration after injury and, in turn, improve functional recovery.