Taxol-induced neuropathy: further ultrastructural studies of nerve fibre changesin situ

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Abstract
Nerve fibre changes have been further monitored morphologically in rat sciatic nerves which had been locally injected with taxol, an antimitotic drug known to promote microtubule assembly. Taxol caused a slowly progressive accumulation of microtubules over a three week period of experimentation, the effect being more pronounced in Schwann cells. Schwann cells of myelinated fibres became detached from nodes of Ranvier and were applied to naked internodes as bulbous cells replete with microtubules and smooth endoplasmic reticulum (ER). In some cases, the smooth ER was believed to arise from rough ER after the displacement of ribosomes. These cells also contained myelin fragments from the original internodes. Microtubules displayed unique relationships with cytoplasmic membranes and were seen to exist as regular 22 nm microtubules, as obliquely sectioned profiles or as incomplete, trough-shaped structures. Internodes devoid of myelin were common, and naked axons covered only by basal lamina appeared swollen and invariably contained an abundance of microtubules. Schwann cells lacking axons had multilobate nuclei and possessed complex arrays comprising smooth ER membranes and microtubules. In areas where microtubules were absent, these membranes compacted to form intracellular myelin. Intermediate filaments existed in lower numbers than normal within both axons and Schwann cells. Arrested mitoses were occasionally seen and it is speculated that together with the immobilization of the cell by the over-abundant polymerization of tubulin, incomplete mitosis was an underlying cause for the observed lack of remyelination over the 21-day period of study. These results suggest that perturbations in microtubule synthesis might dramatically affect Schwann cell behaviour and myelin proliferation.