Neurotoxicity of sodium cyanate. New pathological and ultrastructural observations in Maccaca nemestrina.

The effects of sodium cyanate (NaNCO) on the nervous system of Maccaca nemestrina were studied at 2, 4, and 6 months of administration of the drug. The two groups injected with daily doses of 35 and 25 mg/kg/day of Na-cyanate developed a predominantly demyelinating lesion in the pyramidal tracts of the spinal cord. No neuronal changes were observed in the motor cortex, basal ganglia, midbrain, medulla or anterior horn cells of the spinal cord. There was no evidence of peripheral neuropathy. A comparison between the cyanate induced neuropathy in the rat and in the primate was drawn. Ultrastructurally, both species developed a demyelinating process of central or peripheral myelin characterized by vacuolation of the myelin sheath, removal of myelin debris by macrophages and re-myelination. There was little evidence of axoplasmic damage except for an occasional distended fiber containing abundant dense bodies and whorls of neurofilaments. Oligodendrocytes and Schwann cells were electron microscopically intact and participated actively in remyelination. Maccacas maintained at 15 mg/day and sham animals remained normal clinically and anatomically. The predominantly myelinotoxic effect of cyanate is similar to that produced by other myelinotoxic agents and is attributed to a selective modification of myelin proteins by carbamylation.