Axonopathy and microangiopathy in chronic alloxan diabetes

A significant reduction in the myelinated nerve fiber population was observed during quantitative electron-microscopic examination of peripheral nerves in chronic alloxan diabetic rats. Dystrophic axonal abnormalities and regenerating fibers were more numerous in diabetics than age-matched controls. Schwann cells showed reactive changes including prominent pi granules of Reich and intracytoplasmic filament accumulation. Enumeration of these alterations, however, revealed no significant difference from controls. Endoneurial macrophages in diabetic rats were also filled with lamellar intracytoplasmic inclusions characteristic of a chronic neuropathy. Quantitation of pathologic lesions in teased nerve fibers confirmed the preponderance of axonal over demyelinative disease and showed demyelination to be segmental. Microangiopathy was noted throughout the vasa nervorum of diabetic rats, and quantitative electron microscopy showed endothelial proliferation with doubling of the number of endothelial cells and proportional capillary mural thickening. Swollen, reactive endothelial cells appeared to efface the vascular lumen and may impair capillary perfusion. These microcirculatory changes, in the presence of biochemical and rheologic disturbances may contribute to tissue hypoxia and underly the loss of axons in experimental diabetic neuropathy.