Peripheral axotomy induces neurofilament decrease, atrophy, demyelination and degeneration of root and fasciculus gracilis fibers

We have recently shown that peripheral axotomy by hindlimb amputation in adult cats sequentially results in neurofilament and microtubule decrease and axonal atrophy, myelin wrinkling, myelin remodeling (de- and remyelination), more atrophy and axonal degeneration in proximal sciatic and L7 segmental nerve fibers. The neurophatologic, morphometric and teased fiber alterations in the myelinated fibers (MF) of roots and sampled levels of fasciculus gracilis in groups of adult cats 24 months after hindlimb amputation have now been studied. We found: (1) a severe decrease of neurofilaments, axonal atrophy, myelin wrinkling, de- and remyelination and axonal loss in posterior root axons; (2) that these morphologic abnormalities extended up the fasciculus gracilis in the appropriate territories established from degenerative studies; (3) that the retrograde effect was less severe in ventral root fibers, although atrophy and sprouting were demonstrated here, and (4) that the cellular sequence of retrograde atrophic degeneration of ascending axons was similar to that observed in proximal stump axons. These findings confirm that primary afferent neurons are more vulnerable to axotomy than lower motot neurons and may provide an additional explanation for the poorer functional restoration of sensory than of motor deficit after root compression and in delayed nerve reconnection. Our observations also have important implications for interpretation of neuropathologic alterations in roots and fasciculus gracilis, since the observed features may be secondary to axotomy of peripheral nerve fibers induced by disease and not evidence of a primary derangement.