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 one hour 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 that were also immunoreactive for BDNF or trkB as well as an increase in the length of regenerating axons through allografts from wild type litter mates, both one and two 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.

Experimental Study of Low Dose Ultrashortwave Promoting Nerve Regeneration after Acellular Nerve Allografts Repairing the Sciatic Nerve Gap of Rats

“…The use of autografts is often limited because of graft availability and donor-site morbidity. Acellular nerve allograftstissue engineering nerve grafts of natural peripheral nerve extracellular matrix-are used extensively (English et al 2007;Hu et al (2007); Kim et al (2004). Our former study showed that acellular nerve allografts, treated by hypotonic-chemical detergent (Liu et al 2003), had good biocompatibility and could repair the 10 mm gap of the sciatic nerve in the rat and promote nerve regeneration.…”

Improving Nerve Regeneration of Acellular Nerve Allografts Seeded with SCs Bridging the Sciatic Nerve Defects of Rat

“…A variety of materials, including synthetic and natural materials have attempted to be employed to bridge nerve defects (Evans et al 2002;Keilhoff et al 2003; Smith et al 2004). ANA with component of natural peripheral nerve extracellular matrix are used extensively (Kim et al 2004;English et al 2007;Hu et al 2007). Our former study showed that acellular nerve allografts with preserved basal lamina tubes, treated by hypotonic-chemical detergent (Liu et al 2003), had good biocompatibility and could repair the 10 mm gap of the sciatic nerve in the rat.…”

Evaluation of transcutaneous electrical simulation to improve recovery from corneal hypoesthesia after LASIK

“…English et al showed that if the environment surrounding regenerating axons in peripheral nerves is made deficient in the trkB ligand NT-4/5 by repairing cut nerves with grafts from NT-4/5 mice, the growth of regenerating axons is markedly reduced [17,18]. The explanation of these findings is that the increase in neuronal BDNF and trkB, which is thought to accompany electrical stimulation, forms the basis for a cell autonomous regulation of axon growth [9].…”