NERVE-FIBER REGENERATION FOLLOWING AXOTOMY IN THE DIABETIC BIOBREEDING WORCESTER RAT - THE EFFECT OF ARI TREATMENT

Diabetic neuropathy is characterized by progressive nerve fiber degene ration resulting in nerve fiber loss. In order to examine what role im paired nerve fiber regeneration may play in the progressive net nerve fiber loss, spontaneously diabetic biobreeding Worcester (BB/W) rats w ere subjected to sciatic nerve axotomy at 6 weeks of diabetes. Myelina ted nerve fiber regeneration was examined morphologically and morphome trically at various time points following axotomy. The data were compa red with those of axotomized control rats acid diabetic rats heated wi th an aldose reductase inhibitor (ARI) from 1 week after onset of diab etes. Diabetic rats showed a significant attenuation of nerve fiber re generation during the first 6 weeks following axotomy, which was norma lized at 4 months postaxotomy. ARI treatment resulted in an initial bu rst of supranormal regeneration, which was normalized at 4 months post axotomy. Impaired nerve fiber regeneration in diabetic rats was associ ated with a marked delay in preceding Wallerian degeneration and decre ased phagocytic activity by macrophages, changes not demonstrated in A RI-treated diabetic rats. We propose that the impaired nerve fiber reg eneration in the diabetic BBM rat may, in part, be the result of impai red recruitment and/or function of macrophages necessary for the initi ation of normal nerve fiber regeneration. The corrective effects of AR I treatment on the regenerative ability of diabetic peripheral nerve s uggest that an activated polyol pathway may impact on both intrinsic a nd extrinsic mechanisms, governing nerve fiber regeneration.