Nerve structural defects in diabetic neuropathy: do animals exhibit similar changes?

Abstract

Marked fiber loss and active degeneration of nerve fibers associated with endoneurial microangiopathy ARE characteristic in the peripheral nerve of diabetic patients with advanced stage of neuropathy. These pathological features are not usually found in diabetic animal models. The significance of animal models in the studies of diabetic neuropathy has therefore been questioned because of dissimilarities of neuropathic changes between animal models and human diabetic patients. Scrutinized structural studies with quantitative analysis, however, disclosed modest but significant abnormalities of peripheral nerves in diabetic animal models which well correlated with functional and biochemical alterations. Such pathological findings occurring in diabetic animal models may be the consequences of hyperglycemia, and possibly be interpreted as early signs of diabetic neuropathy or tissue adaptation to hyperglycemia. In addition, recent experimental studies demonstrated significant nerve fiber degeneration in the peripheral nerve of diabetic rats when they were superimposed with local ischemia or systemic hypoglycemia, suggesting the vulnerability of diabetic nerve to environmental insults. Continuous hyperglycemia, probably through an enhanced polyol pathway and/or increased non-enzymatic glycation may underlie the vulnerability of nerve. Diabetic animals thus serve as a valuable asset for the exploration of metabolic effects on the subcellular structures of the peripheral nerve and for the development of effective treatment regimens for diabetic neuropathy. © 1997 John Wiley & Sons, Ltd.