Ultrastructural alterations of the rabbit sciatic nerve, spinal cord and cerebellum, following methionine sulphoximine administration.

Methionine sulphoximine (MSO) is a centrally acting neurotoxin which inhibits the glutamate metabolism enzymes and has convulsive properties. Small doses of MSO were administered to rabbits, either intravenously (i.v.) or intracerebroventricularly (ICV), and electron microscopic examination of the cerebellum, the spinal cord and the sciatic nerve was performed on the first day of rabbit hind leg rigid paralysis (myopathy with histological findings resembling myositis), which set in by the 2nd to 4th day after MSO administration. In the cerebellum focal minor alterations were found in the astrocytes (swelling and lucidity, diminution of glycogen granules) and sparsely in the presynaptic terminals (lucidity and clumping), whereas most of the neuron presented a normal appearance. In the spinal cord and in the sciatic nerve a dissociation of the axon from the myelin sheath was evident in a small number of myelinated nerve fibres, along with the appearance of vacuolated spaces. Mitochondrial disorganisation in the axons, as well as glial cell alterations, were also seen. The ultrastructural alterations were non specific, and since they were induced 2 to 4 days after the administration of either minimum doses (i.v.) or of extremely low doses (ICV) of MSO, they may be attributed to the inordinate increase of metabolism during the period of convulsions.