SCHWANN-CELL CHANGES INDUCED AS EARLY AS ONE WEEK AFTER GALACTOSE INTOXICATION

In galactose neuropathy, aldose reductase inhibitor (ARI)-preventable Schwann cell injury has been reported in studies in which galactose fe eding continued over a period of months. Given the link between these morphologic changes and polyol pathway flux, polyol accumulation after just days of galactose feeding points to the possibility that structu ral changes occur much earlier than previously reported. The aim of th is study was to examine rat sciatic nerve after 7 days of galactose fe eding for evidence of myelinated fiber injury and establish whether it is related to polyol accumulation. Compared to control of ART-treated galactose-fed rats, nerves from untreated galactose-fed rats had incr eased water (P < 0.05) and dulcitol (P < 0.008) content and decreased amounts of myo-inositol (P < 0.01). Electron microscopy revealed re ac tive Schwann cell changes in myelinated fibers characterized by increa sed cytoplasmic volume, and the occurrence of lipid droplets, pi granu les of Reich and enlarged mitochondria. Dystrophic accumulation of int ermediate filaments was also observed in the inner glial loop. Degener ative changes included periaxonal swelling, enlarged mitochondria with out recognizable cristae, lysis of Schwann cell cytoplasm and demyelin ation. Reactive (P < 0.05) and degenerative (P < 0.01) changes as well as the number of redundant basal lamina profiles (P < 0.05) were sign ificantly more frequent in untreated galactose-fed rats compared to co ntrols. ARI treatment attenuated these changes. Consistent with the in itial stages of onion-bulb formation, profiles with imbricate Schwann cells were also seen only in untreated galactose-fed rats. The finding s suggest that short-term increases in polyol pathway activity can hav e deleterious effects on Schwann cells of myelinated fibers.