Taxol-induced neuropathy after nerve crush: long-term effects on regenerating axons

Previous studies have shown that newly derived axonal sprouts are sensitive to the effect of taxol. Taxol induced an accumulation of microtubules in axonal sprouts, which resulted in giant axonal bulbs with the subsequent excessive proliferation of distorted axonal twigs from the distal end of swollen axonal bulbs 3 weeks after the nerve crush. The present study was performed to evaluate the chronic effects of taxol upon regenerative axons and the morphological changes have now been followed up to 40 weeks post injection (PI). The results showed that 1 month PI, the giant axonal bulbs with the conglomerations of haphazardly arranged axonal twigs were numerous at the lesion site. Later on, the axonal twigs, filled with axoplasmic microtubules, elongated and showed more longitudinal orientation as they grew distally. After 8 weeks PI the axonal elongation progressed and the majority of the original small axonal twigs disappeared and several larger diameter axonal branches developed. Some of the axonal branches emerging from the giant axonal bulbs became myelinated and survived while others degenerated. Ultrastructurally, the number of microtubules remained high in the surviving axonal branches up to 3 months PI. The degenerating branches showed an unexpected loss of microtubules 2 months onwards with the subsequent accumulation of degenerative axoplasmic material. However, neurofilaments were numerous in the degenerating axonal branches even when degenerative axoplasmic material was present. The present results show that some of the taxol-induced axonal twigs develop into larger diameter axonal branches which persist for up to 10 months. The cytoskeletal differences in the surviving versus the degenerating axonal branches suggests local regulatory mechanisms for regulation of axonal cytoskeleton in axons.(ABSTRACT TRUNCATED AT 250 WORDS)