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The peripheral axons of lower motor and spinal ganglion neurons were permanently transected and not allowed to regrow to target tissue in adult cats by amputation of the hind limb at the hip. The number and sizes of L-7 lower motor neurons at two levels (cell bodies of lateral group motor neurons and myelinated fibers [MFs] of ventral root) and of L-7 spinal ganglion neurons at two levels (cell bodies of L-7 spinal ganglion and MFs of dorsal root) were morphometrically evaluated in groups of cats at 3 months, 9 months, and 18 months after amputation and compared with the number and sizes of neurons in controls or with those on the opposite side. The number of neurons decreased only minimally after amputation. The diameter of neuron cell bodies was only equivocally reduced. By contrast, the median diameter and the peak diameter of both large and small MFs of dorsal and ventral nerve roots were significantly (approximately 30%) less than those of controls. This reduction in diameter of MFs is judged to be related to chronic axonal atrophy rather than to selective loss of large fibers. Permanent transection of distal axons should therefore prove to be a good model of chronic axonal atrophy.

Alterations of primary afferent axons in the nucleus gracilis were studied at three weeks and four, 12, and 24 months after peripheral nerve axotomy by hindlimb amputation at the hip joint in 19 female cats. The contralateral side and two cats not subjected to amputation were controls. We observed two major types of fiber alterations. One, fibers showed changes of axonal atrophy, myelin remodelling, and degeneration. Adaxonal invagination occurred more frequently (p less than 0.005) at three weeks postamputation, in territories known to contain centrally directed axons of primary afferent neurons of the lower limb, than in controls. Perhaps adaxonal sequestration contributed to axonal attenuation. Two, there were filamentous, granular, central core, and other types of axonal swellings found in territories containing central axons of primary afferent neuron terminals of the lower limb. These changes occurred most frequently at 12 and 24 months and were significantly more frequent than in control tissue. These reactive/dystrophic axons therefore were associated with permanent axotomy, but we have not established that they occur in central axons of primary afferent neurons, or whether they are degenerative or abortive regenerative changes.

Feeding galactose to rats induces nerve conduction abnormalities, increased levels of nerve galactitol, endoneurial edema, elevated pressure and hypoxia of endoneurial fluid, and pathological abnormalities of nerve fibers. To investigate the cellular mechanisms of the fiber lesions and their possible relationship to alterations in the nerve microenvironment, rat peroneal nerves were morphometrically evaluated eight months after the commencement of galactose feeding. Whereas the density of neurofilaments (NF/micron2) in the transverse axonal area of myelinated fibers was not significantly different between the nerves of galactose-fed and control rats, axonal areas and the number of NF/axon, when related to myelin spiral length, were significantly less in nerves of galactose-fed rats. Myelin alterations, characteristic of axonal atrophy, were also significantly increased. The present data provide evidence of a proportionate decrease in axonal caliber and the number of NF/axon in myelinated fibers in experimental galactose neuropathy, suggesting that galactose induces fibers in experimental galactose neuropathy, suggesting that galactose induces either decreased NF synthesis, assembly or transport. The possible role of microenvironmental alterations, including endoneurial hypoxia and hyperosmolarity, in the production of this axonal atrophy is discussed.

To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression--e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament.