Brief Electrical Stimulation Promotes the Speed and Accuracy of Motor Axonal Regeneration

Abstract

Functional recovery is often poor despite the capacity for axonal regeneration in the peripheral nervous system and advances in microsurgical technique. Regeneration of axons in mixed nerve into inappropriate pathways is a major contributing factor to this failure. In this study, we use the rat femoral nerve model of transection and surgical repair to evaluate (1) the effect of nerve transection on the speed of regeneration and the generation of motor-sensory specificity, (2) the efficacy of electrical stimulation in accelerating axonal regeneration and promoting the reinnervation of appropriate muscle pathways by femoral motor nerves, and (3) the mechanism of action of electrical stimulation. Using the retrograde neurotracers fluorogold and 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 parent axons proximal to the repair site dramatically reduces this period (to 3 weeks) and accelerates PMR. (3) The positive effect of short-term electrical stimulation is mediated via the cell body, implicating an enhanced growth program. The effectiveness of such a short-period low-frequency electrical stimulation suggests a new therapeutic approach to accelerate nerve regeneration after injury and, in turn, improve functional recovery.

Estimations of topographically correct regeneration to nerve branches and skin after peripheral nerve injury and repair

“…The regeneration rates to the tibial nerve branch (between 75-95%) two months after nerve section and suture are in good agreement with previous studies suggesting that most of the neurones have survived and regenerated to the nerve branches after the nerve injury (Fritzsch and Sonntag, 1991;Al-Majed et al, 2000), and also with findings suggesting that sensory neurons regenerate better than motoneurons (Suzuki et al, 1998;Negredo et al, 2004). A smaller proportion of sensory neurones regenerated to the skin of the third digit (59%).…”

On the use of fast blue, fluoro-gold and diamidino yellow for retrograde tracing after peripheral nerve injury: uptake, fading, dye interactions, and toxicity

“…A loss of about 20 to 30% hypoglossal motoneurones (Snider and Thanedar, 1989;Törnqvist and Aldskogius, 1994) and facial motoneurones (Yu, 1988;Mattson et al, 1998) was described after cranial nerve section in adult rats. Several authors found a non-significant loss of about 10% motoneurones after sciatic nerve injury (Vanden-Noven et al, 1993;Lowrie et al, 1994;Valero-Cabré et al, 2001) and no changes with respect to the contralateral side was found after section and repair of the rat femoral nerve (Al-Majed et al, 2000).…”

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].…”