Improvement of Peripheral Nerve Regeneration following Immunological Demyelination In Vivo

BACKGROUND: To improve regeneration of the peripheral nervous system, a therapy was utilized in the adult rat sciatic nerve in which nerve regeneration is enhanced following acute crush injury. The authors hypothesized that (1) axon regeneration within a region of injury increases following experimental, immunological demyelination; and (2) regenerated axons partially derive from the proximal motor axons. METHODS: The sciatic nerves of 10 Sprague-Dawley rats were injected with a demyelinating agent following crush injury, while the nerves of 10 control rats received a crush injury without therapy. The sciatic nerves were harvested at 14 and 28 days. The lesion containing length of the nerve was cut into 1-mm blocks, and specimens were fixed and evaluated using structural and immunohistochemical analyses. A Flouro-Ruby tracer was injected into the sciatic nerves of a separate group of rats to determine the source of axonal regrowth. RESULTS: An epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 14 days, remyelination was demonstrated spanning the injured sciatic nerve segment. At 28 days, peripheral nerve regeneration was quantified by total axon count, axon density, and nerve fiber diameter. Tracers demonstrated that regeneration arose partially from proximal motor axons. CONCLUSIONS: This study demonstrates enhanced regeneration in the peripheral nervous system using experimental, immunological demyelination. Findings indicate that axon count, axon density, and nerve fiber diameter within a region of acute crush injury in the rat sciatic nerve can be improved using a demyelinating treatment.