GALACTOSEMIA PRODUCES ARI-PREVENTABLE NODAL CHANGES SIMILAR TO THOSE OF DIABETIC NEUROPATHY

The present study was designed to examine the development of structura l changes, characteristic of diabetic neuropathy, in chronic galactose mia and their responsiveness to inhibition of the polyol-pathway. Spra gue-Dawley rats weighing 70-90 g were given a 50% galactose diet conti nued for 4 or 8 months. Half of these animals were simultaneously give n the aldose reductase inhibitor (ARI) WAY 121-509. ARI-treatment norm alized galactitol and myoinositol levels in the sciatic nerve. At 4 mo nths, sciatic nerve conduction velocity (NCV) in galactosemic rats was reduced by 30% which was prevented in ARI-treated rats. At 8 months g alactosemia reduced NCV to 58% of control values, while ARI-treatment for 8 months improved NCV to 71% of control values. ARI-treatment prev ented in galactosemic rats nodal structural changes characteristic of diabetic neuropathy, whereas axonal atrophy was not affected by ARI-tr eatment, which may in part account for the only partial prevention of the NCV slowing at 8 months. Nerve fiber regeneration was increased 4- fold in ARI-treated rats compared with untreated galactosemic rats. Th ese data suggest that chronic galactosemia produces a neuropathy struc turally similar to diabetic neuropathy. The lack of an ARI-treatment e ffect on axonal atrophy suggests that this defect is not polyol relate d in galactosemia.