ULTRASTRUCTURAL ALTERATIONS OF THE RABBIT SCIATIC-NERVE, SPINAL-CORD AND CEREBELLUM, FOLLOWING METHIONINE SULFOXIMINE ADMINISTRATION

Methionine sulphoximine (MSG) is a centrally acting neurotoxin which i nhibits the glutamate metabolism enzymes and has convulsive properties . Small doses of MSO were administered to rabbits, either intravenousl y (IV) or intracerebroventricularly (ICV), and electron microscopic ex amination of the cerebellum, the spinal cord and the sciatic nerve was performed on the first day of rabbit hind leg rigid paralysis (myopat hy with histological findings resembling myositis), which set in by th e 2nd to 4th day after MSO administration. In the cerebellum focal min or alterations were found in the astrocytes (swelling and lucidity, di minution of glycogen granules) and sparsely in the presynaptic termina ls (lucidity and clumping), whereas most of the neuron presented a nor mal appearance. In the spinal cord and in the sciatic nerve a dissocia tion of the axon from the myelin sheath was evident in a small number of myelinated nerve fibres, along with the appearance of vacuolated sp aces. Mitochondrial disorganisation in the axons, as well as glial cel l alterations, were also seen. The ultrastructural alterations were no n specific, and since they were induced 2 to 4 days after the administ ration of either minimum doses (IV) or of extremely low doses (ICV) of MSG, they may be attributed to the inordinate increase of metabolism during the period of convulsions.