Immunohistochemical Studies of Experimental Diabetic Neuropathy

Accumulations of substance P, somatostatin, vasoactive intestinal polypeptide (VIP) and dopamine-/3-hydroxylase (DBH) after ligation of the ischiadic nerve of streptozotocininduced diabetic rats were observed by an immunohistochemical technique and the results were examined both qualitatively and quantitatively. Besides, effects of administration of an aldose reductase inhibitor (ONO 2235), a key enzyme for polyol synthesis, on these accumulation patterns were studied. Immunofluorescent positiveness of these biological active substances was intensely observed along the axon in nerves of control animals. In the ischiadic nerves of diabetic rats, it was weakly observed in irregular shapes. On the other hand, in the ischiadic nerve of the diabetic rat treated with the aldose reductase inhibitor, substance P-, DBH- and VIP- immunoreactive positiveness was recovered in both distribution pattern and accumulation length. Our findings show that there are abnormalities of the axonal flow of the peripheral nerve in diabetic animals. These results also suggest that polyol pathway activity may contribute to the pathogenesis of diabetic neuropathy and ONO-2235 may be useful in preventing diabetic complications.