Joseph H. Boyes Award. Dispersion of regenerating axons across enclosed neural gaps

Abstract

Tubular prostheses support peripheral axon regeneration across gaps of up to 3 cm in the primate. However, the precision with which axons cross a gap and reinnervate the periphery remains controversial. These experiments use continuous tracing of regenerated rat sciatic nerve axons with HRP-WGA to examine the dispersion of axons as they cross a gap, and the effects on this dispersion of gap distance and fascicular orientation. Proximal and distal tibial and peroneal fascicles were precisely oriented about the longitudinal midplane of a silicon tube, with correct or reversed fascicular alignment and gaps of 2 mm and 5 mm. After 6 weeks of regeneration, HRP-WGA was applied to the distal peroneal fascicle to continuously label its reinnervating axons. These axons tended to grow straight across the tube, with dispersion increasing as a factor of distance when correct fascicular alignment was maintained. However, when fascicular alignment was reversed, axonal dispersion was determined by fascicular size rather than fascicular identity. These experiments provide no evidence for neurotropic interactions promoting "correct" fascicular reinnervation. Progressive axonal dispersion and the absence of factors to promote fascicular specificity should result in an increase of random reinnervation and functional disruption with larger gaps. An enclosed gap is not an acceptable substitute for nerve graft when reconstructing a nerve that serves multiple functions.