Immunological demyelination enhances nerve regeneration after acute transection injury in the adult rat sciatic nerve

Abstract

Introduction: Our recent experiments demonstrate that demyelination enhances peripheral nerve regeneration after contusion injury in the adult rat sciatic nerve. The role of demyelination in peripheral nerve regeneration in a sciatic nerve transection model has yet to be elucidated. We hypothesize that (1) axon regeneration within a region of injury increases after experimental, immunologic demyelination, and (2) regenerated axons are partially derived from the proximal motor axons.

Methods: Sciatic nerves of adult female Sprague-Dawley rats (n = 20) were injected with a demyelinating agent immediately after transection injury. The sciatic nerves were harvested 1 month (n = 5) and 2 months (n = 5) after surgery. In the control groups, the cut nerves were reapproximated without demyelination therapy. The lesion containing length of nerve was cut into 1-mm transverse blocks and processed to preserve orientation. Specimens were evaluated using structural and immunohistochemical analyses.

Results: A single epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 1 month, remyelination was clearly shown throughout the injured sciatic nerve segment. At 2 months, there was a statistically significant increase in peripheral nerve regeneration following demyelination therapy as evidenced by total axon count, axon density, and fiber diameter.

Conclusion: This study demonstrates enhanced histomorphologic nerve regeneration in the rat sciatic nerve after local delivery of experimental, immunologic demyelination following transection injury. It highlights the utility of demyelination in peripheral nerve regeneration. This therapy may be applicable for tissue-engineered constructs, cell-based systems, and nerve transfers to improve outcomes in peripheral nervous system injuries.