Electrical stimulation promotes peripheral axon regeneration by enhanced neuronal neurotrophin signaling

TLDR

Electrical stimulation of cut peripheral nerves at the time of surgical repair enhances axon regeneration. The study examined whether this enhancement arises from increased cell‑autonomous neurotrophin signaling within axons or from neurotrophins produced in the surrounding environment. Axon regeneration through nerve allografts was used to assess the contribution of axonal versus environmental neurotrophin signaling. Electrical stimulation increased BDNF/trkB‑positive dorsal root ganglion neurons and axon length through allografts in wild‑type mice, promoted growth through neurotrophin‑4/5 knockout or acellular grafts, but had no effect in NT‑4/5 knockout mice, demonstrating that the benefit depends on axonal trkB signaling rather than environmental neurotrophin production. © 2006 Wiley Periodicals, Inc., Develop Neurobiol 67:158–172, 2007.

Abstract

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. © 2006 Wiley Periodicals, Inc. Develop Neurobiol 67: 158–172, 2007.