EXPERIMENTAL GERMANIUM DIOXIDE-INDUCED NEUROPATHY IN RATS

We report an experimental model of germanium dioxide (GeO2)-induced ne uropathy in rats. More than 6 months administration of GeO2 to young r ats produced neuropathy characterized by segmental demyelination/remye lination and nerve edema. Electron microscopic studies demonstrated th at changes in Schwann cells, such as an increased cytoplasmic volume o r disintegration of the cytoplasm, were the earliest pathological find ings. Schwann cell mitochondria contained high electron-dense material s. Subsequent removal of necrotic Schwann cell debris and myelin by in vading macrophages was evident. These findings suggested that the Schw ann cells themselves are the primary target of the toxin. The depositi on of electron-dense granules in the intra-axonal vesicles, which was suggestive of glycogen granules in mitochondria, was observed in the a dvanced stage of the neuropathy. The findings of endoneurial edema wit h splitting of myelin lamellae were noted at the early stage of demyel ination. Nerve edema may be the result of GeO2-induced endothelial cel l injury.