Some observations on the experimental production of acute neuroaxonal and synaptosomal dystrophy.

Abstract

Fluorocitrate, and fluoroacetate block the Krebs cycle in neural tissue, cause convulsive seizures, and produce interesting neuropathological lesions, notably a swelling of neuronal and glial mitochondria and neuroaxonal and synaptosomal dystrophy. Axonal ballooning is a consequence of convulsive seizures coupled with inhibition of the Krebs cycle. Mg++ suppresses the convulsive seizures produced by fluorocitrate and prevents axonal ballooning. Strychnine convulsions do not cause neuroaxonal dystrophy. However, Mg++ does not prevent mitochondrial swelling or axonal dystrophy. Fluorouracil produces similar neuropathological lesions, apparently because it is degraded partly to fluoroacetate. Numerous agents with diverse biological actions also produce dystrophic changes in axons and nerve endings. These include: cyanide, arsenious oxide, ouabain, puromycin, parabenzoquinone, malonate, succinate, 3-acetylpyridine, desoxypyridoxine, methionine sulfoximine, antimycin A, iminodiproprionitrile, plasmocide, pyrathiamine, cupric sulfate, Trypan blue. Electron microscopic examination showed that the following agents also caused mitochondrial swelling: cyanide, iminodiproprionitrile, plasmocide, 3-acetylpyridine, methione sulfoximine, puromycin and Trypan blue. It is proposed that a swelling of perikaryal mitochondria is the common basis for the increased disgorgement of lysosomes, mitochondria and other cytoplasmic constituents occurring in neuroaxonal and synaptosomal dystrophy.