Ultrastructural evidence of peripheral neuropathy in spontaneous hyperglycemic Otsuka Long-Evans Tokushima Fatty rats: histopathological similarity to human diabetic neuropathy

The ultrastructure in the peripheral nerves of spontaneous hyperglycemic rats and of two cases of human diabetic neuropathy was compared using electron microscopy. Experimental animals were Otsuka Long-Evans Tokushima Fatty (OLETF) rats, bred to reveal spontaneous hyperglycemia and glucosuria after 20 weeks of age. The ultrastructural findings in the peripheral nerves of OLETF rats consisted of destructive changes of the myelin sheath, followed by axonal degeneration and basal laminal thickening of Schwann cells covering small-caliber axons. These alternations in the endoneurium were associated with the later onset of capillary vasculopathy, which revealed duplication of endothelial basal lamina and proliferation of microvilli at the luminal surface. It was characteristic that these histological alterations were apparently distinguished according to the duration of hyperglycemia between 10 and 30 weeks of age. The two human diabetic cases, who had suffered from non-insulin-dependent diabetes mellitus (NIDDM) for a considerable period, had undergone amputation of the leg following the onset of severe neuropathic ulcerative necrosis. Biopsied specimens from peripheral nerves revealed perineurial thickening, proliferation of endoneurial collagen tissue, loss of myelinated fibers, extension of Schwann cell processes with occasional onion-bulb formation, and endoneurial vascular basal laminal thickening. The results of these comparative histological studies suggested that the alterations occurring in peripheral nerve tissue of experimental diabetic OLETF rats may reflect the early pathological changes of human diabetic neuropathy.