Electrical stimulation promotes peripheral axon regeneration by enhanced neuronal neurotrophin signaling

Abstract

Electrical stimulation of cut peripheral nerves at the time of their surgical repair results in an enhancement of axon regeneration. Regeneration of axons through nerve allografts was used to evaluate whether this effect is due to an augmentation of cell autonomous neurotrophin signaling in the axons or signaling from neurotrophins produced in the surrounding environment. In the thy-1-YFP-H mouse, a single 1 h application of electrical stimulation at the time of surgical repair of the cut common fibular nerve results in a significant increase in the proportion of YFP+ dorsal root ganglion neurons, which were immunoreactive for BDNF or trkB, as well as an increase in the length of regenerating axons through allografts from wild type litter mates, both 1 and 2 weeks later. Axon growth through allografts from neurotrophin-4/5 knockout mice or grafts made acellular by repeated cycles of freezing and thawing is normally very poor, but electrical stimulation results in a growth of axons through these grafts, which is similar to that observed through grafts from wild type mice after electrical stimulation. When cut nerves in NT-4/5 knockout mice were electrically stimulated, no enhancement of axon regeneration was found. Electrical stimulation thus produces a potent enhancement of the regeneration of axons in cut peripheral nerves, which is independent of neurotrophin production by cells in their surrounding environment but is dependent on stimulation of trkB and its ligands in the regenerating axons themselves.

Effects of acute selective pudendal nerve electrical stimulation after simulated childbirth injury

“…Electrical stimulation has been demonstrated in rat femoral nerves to increase intrinsic BDNF and NT-4 expression in injured motoneurons and promote neuroregeneration after injury (2,15). In this study, a statistically significant upregulation of BDNF mRNA in the stimulated Onuf's nucleus was noted both 2 days and 1 wk after injury and stimulation compared with the shamstimulated side.…”

“…Electrical stimulation has been demonstrated to promote neuroregeneration after injury and to increase intrinsic BDNF expression in injured neurons (1,2,15,19). Stimulation could therefore provide a method for facilitation of recovery by promoting neuroregeneration and reinnervation if the muscle is damaged simultaneously, such as in childbirth injury.…”

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

“…7c) [7]. Using transgenic mice that express yellow fluorescent protein in a small proportion of their axons and by cross-breeding of these mice with mice in which neurotrophic factor expression was deleted, English et al [66] demonstrated the critical role of the neurotrophic factors brainderived neurotrophic factor (BDNF) and neurotrophin 4/5 in the efficacy of the electrical stimulation effect in accelerating nerve regeneration [66]. Exogenous administration of either BDNF or GDNF did not increase nerve regeneration after immediate nerve repair (Fig.…”

Effect of slope and sciatic nerve injury on ankle muscle recruitment and hindlimb kinematics during walking in the rat

“…Several strategies that enhance axon regeneration after peripheral nerve transection have been identified, e.g. proteoglycan degradation (Groves et al, 2005), electrical stimulation (Al-Majed et al, 2000;English et al, 2007) and exercise (Sabatier et al, 2008), but far less is understood about whether function is restored when axon regeneration is enhanced (Varejao et al, 2004). A better understanding of the slope-related specificity of muscle activation and hindlimb control in intact and injured animals may help in efforts to identify strategies that ultimately enhance function.…”