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.