Number, size, and class of peripheral nerve fibers regenerating after crush, multiple crush, and graft

Morphometric characterization of fiber regeneration in a distal nerve after focal proximal nerve injury may provide useful clinical information and insights about underlying neurobiologic mechanisms. The myelinated (MF) and unmyelinated (UF) fibers of peroneal nerve of groups of mice were assessed 9 months after crush, graft, and multiple crush injury of the proximal sciatic nerve: number and size distribution of axon areas, myelin areas, and fiber diameters. After crush, number of regenerated MF and UF was almost identical to that of controls. Their size distribution had almost returned to normal. After graft and multiple crush, fiber number had returned to normal or was significantly increased beyond normal but there were only a few large fibers present. This may be explained by: (a) disproportionate regeneration of small-diameter compared to large-diameter classes of fibers; (b) misdirected regrowth of fibers, so that functional reinnervation was not established, resulting in failure of development or retrograde atrophy and degeneration; or (c) cellular alterations at the site of injury or in the distal nerve which inhibited neural outgrowth or elongation or did not inhibit outgrowth but retarded or prevented maturation. We conclude that explanation (b) is involved, and that there is some evidence favoring the roles of (a) and (c).