The long-term effects of a single injection of taxol upon peripheral nerve axons.

Abstract

To study the long-term effects of a single injection of the microtubule stabilizing drug taxol in vivo, the compound was injected into rat sciatic nerve and the ensuing morphological changes followed for 8-25 weeks after injection. In accord with previously published works, taxol-induced giant axonal bulbs were common and were most marked at 8-10 weeks. From 12 weeks onwards these giant axons decreased in diameter with concomitant remyelination. By 20 weeks axonal bulbs could not be seen. The recovery of axons from taxol intoxication began 8-12 weeks after injection with the growth of axonal sprouts, longitudinally and laterally, from the distal aspect of the proximal stump. During recovery, from 12 weeks onwards, axons showed apparent reorganization of the axoplasmic cytoskeleton where microtubules diminished and neurofilaments became more numerous. By 16 weeks only small groups of microtubules remained, often encircling a mitochondrion. By 25 weeks taxol-treated nerves showed no apparent taxol-induced changes. A common ultrastructural finding up to 16 weeks was the appearance within axons of tubular profiles covered by a double membrane. These structures were sometimes arranged as crystalloid aggregates. The diameter of these profiles was 85 nm, they were most common at 12 weeks and it is proposed that they may be derived from mitochondria. The present results show taxol to have a long-lasting and local effect upon axoplasmic organization in vivo. The cytoskeletal reorganization described supports the concept of the differential movement of axoplasmic neurofilaments and that neurofilaments stabilize axonal structures.