The acute effects of taxol upon regenerating axons after nerve crush.
The effects of taxol, a compound renowned for its ability to promote microtubule assembly, were studied upon axons after its injection into rat sciatic nerve immediately following a local nerve crush injury. The single injection of taxol was delivered into the lesion site and the animals were sampled up to 4 weeks post-injection (PI) for morphological study. At the lesion site, Wallerian degeneration was encountered and this was followed by axonal sprouting by 5 days PI. In contrast to axonal sprouting seen in uninjected controls (crush-only), sprouts in taxol-injected nerves rapidly became swollen due to an increasing number of axoplasmic microtubules. By 2 weeks PI, this led to the formation of giant axonal bulbs from which by 3 weeks PI, a secondary wave of regenerative growth occurred consisting of thin, haphazardly twisted axonal twigs largely lacking Schwann cell investment. These were most numerous after 3 and 4 weeks PI. Within the affected axoplasm, microtubules occasionally formed occasional channels around mitochondria. The present results, characterized by the more rapid appearance of taxol-induced giant axonal bulbs in regenerating sprouts than seen after taxol injection of intact nerve, suggest that regenerating PNS axons are exquisitely sensitive to and dramatically affected by taxol. The conclusions support previous observations on a crucial role for microtubules during early axonal growth.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000648:ultrastructure; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D008854:Microscopy, Electron; D008870:Microtubules / Q000648:ultrastructure; D009186:Myelin Sheath / Q000648:ultrastructure; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D017239:Paclitaxel; D013997:Time Factors
D000470:Alkaloids; D017239:Paclitaxel; D004121:Dimethyl Sulfoxide