Multiple Applications of 20Hz electrical Stimulation After Peripheral Nerve Injury Promote Motor Axon Regeneration And Retention of Exaggerated H Reflexes

Abstract

Exercise promotes regeneration of axons, and a single electrical stimulation can mimic the effect of exercise. A single treatment with one hour of 20 Hz continuous electrical stimulation promotes the regeneration of axons in cut peripheral nerves. This enhanced axon regeneration is the result of a transient increase in neuronal expression of BDNF and its trkB receptor (Al-Majed et al, 2000). A slightly more robust enhancement of peripheral axon regeneration is achieved by two weeks of daily treadmill exercise, also in a BDNF/trkB-dependent manner. We tested the hypothesis that multiple applications of brief electrical stimulation (mES) would be more effective in promoting functional muscle reinnervation than a single application (ES). Sciatic nerves of C57B6 mice were cut and repaired by end-to-end anastomosis. At the time of nerve repair and every third day for the following two weeks, the proximal segment of the cut nerve was stimulated continuously for one hour at 20 Hz. In control groups used for comparison, nerves were cut and repaired and mice were either untreated (UT) or treated with a single application of electrical stimulation (ES) at the time of nerve repair. Beginning two weeks later, functional muscle fiber reinnervation was assayed using stimulus evoked EMG activity from the gastrocnemius and tibialis anterior muscles. Direct muscle (M) responses and monosynaptic H reflexes produced in response to sciatic nerve stimulation above the injury site were studied in awake animals. The amplitude of M responses recorded from reinnervated muscles increased progressively over the 14 week post transection study period. In the mES animals, this increase was more rapid than UT mice but not significantly different from ES mice. In mES mice, the amplitude of H reflexes recorded from reinnervated muscles increased more rapidly than found in UT mice, but not ES mice, reaching a peak at six weeks after nerve injury. The H reflexes in the mES and ES animals were maintained at more than twice the amplitude of the same reflexes recorded prior to injury for the remaining eight weeks studied. Repeated ES does enhance motor axon regeneration and functional muscle reinnervation, and this enhancement is more robust than a single ES treatment. mES also results in the retention of exaggerated H reflexes.