Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model

Shih-Tien Hsu,Chun-Hsu Yao,Yuan-Man Hsu,Yung-Hsiang Chen,Jia-Horng Lin,Yueh-Sheng Chen

doi:10.1038/srep42280

Abstract

Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury.

Highlights

Taxol, a microtubule-binding compound, is one of the commonly used antineoplastic drugs for the treatment of solid tumours
To determine this effect with a standard accepted acute injury model of neuropathy[11,12]; we assessed the influence of taxol on a 10 mm sciatic nerve defect in rats, which was repaired with a silicone rubber nerve tube
Since the regenerative ability of nerves strongly relies on the regulation of growth factors and immune responses, the expression levels of nerve growth factor (NGF), platelet-derived growth factor (PDGF), and immunoregulatory factors, including tumour necrosis factor (TNF)α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and CD68, were investigated in the regenerated nerves

Summary

Introduction

Taxol (paclitaxel), a microtubule-binding compound, is one of the commonly used antineoplastic drugs for the treatment of solid tumours. It appears that the effects of microtubule stabilization by taxol on the neuron are dependent on the degree of stabilization This is noted by recent studies describing taxol as a candidate treatment for promoting regeneration after central nervous injury. Conflicting results on nerve injury/regeneration have been reported, and little information was found in the literature to examine the effect of taxol on the regeneration of injured peripheral nerves To determine this effect with a standard accepted acute injury model of neuropathy[11,12]; we assessed the influence of taxol on a 10 mm sciatic nerve defect in rats, which was repaired with a silicone rubber nerve tube. Expression levels of calcitonin gene-related peptide (CGRP) in the lumbar spinal cord were determined These procedures were performed with the aim of elucidating the mechanisms underlying the observed effects of taxol treatment. Since the regenerative ability of nerves strongly relies on the regulation of growth factors and immune responses, the expression levels of nerve growth factor (NGF), platelet-derived growth factor (PDGF), and immunoregulatory factors, including tumour necrosis factor (TNF)α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and CD68, were investigated in the regenerated nerves

Methods

Results

Conclusion