Taxol-induced neuropathy after nerve crush: long-term effects on Schwann and endoneurial cells

Abstract

The present investigation is a continuation of previous studies showing taxol-induced changes up to 4 weeks after a nerve crush. To evaluate the long-term cellular response to taxol, we have extended our morphological analysis of these changes in the taxol-treated nerve crush for up to 40 weeks after a single injection of taxol (PI). The results showed that Schwann cells exhibited a long-lasting and marked response when taxol was injected into the crushed peripheral nerve. During the first 2 months PI, taxol-induced giant axonal bulbs showed the formation of primitive nodes of Ranvier as a result of Schwann cell invaginations. The Schwann cell invaginations developed into nodes of Ranvier after 3-4 months PI together with the recovery of axonal bulbs. Ultrastructurally, cytoplasmic microtubule-related abnormalities were numerous up to 3 months PI and microtubules were seen to enclose degenerative myelin. Taxol-induced abnormalities in Schwann cells did not prevent their ability to produce myelin sheaths, although the accumulation of microtubules between myelin lamellae caused swellings of Schmidt-Lanterman incisures and paranodal myelin loops. Abnormal, extracellular collagen-like 5-nm-thin fibrils were noted closely associated with Schwann cells up to 10 weeks PI. Endoneurial cells, present as long rows without interconnections were noted in areas devoid of axonal sprouts up to 6-8 weeks PI. These cells showed marked cytoplasmic elongations and were covered by thickened basal lamina and contained several microtubule-related cytoplasmic structures, some of which have not been described previously. Taxol, when injected into crushed sciatic nerve induced a long-lasting response upon the Schwann cells with several ultrastructural abnormalities which correlate with changes in myelination and the development of nodes of Ranvier. These findings suggest that normal microtubule turnover is necessary for Schwann cells during nerve fiber regeneration.