Cavaletti G, Tredici G, Braga M, Tazzari S
Institute of Human Anatomy, University of Milan, Italy.
Exp Neurol. 1995 May;133(1):64-72. doi: 10.1006/exnr.1995.1008.
Taxol, a natural extract with antineoplastic properties, is known to be neurotoxic in humans. Its neurotoxicity after systemic administration, however, has never been studied in detail at the morphological level in humans and in animals. In this study we administered taxol intraperitoneally to female Wistar rats and we performed an extended neurophysiological and morphological examination of the peripheral nerves, dorsal root ganglia, spinal rootlets, and spinal cord. The results obtained in this experimental model indicate that taxol induces pathological changes mainly in the peripheral nerves, but they are present also in the ventral and dorsal spinal rootlets and spinal dorsal column fibers. The dorsal root ganglia and spinal cord neurons were, on the contrary, unaffected. The most impressive change induced by systemic taxol administration was intraaxonal neurotubule accumulation. Schwann cells showed signs of "activation" but clear demyelination was not observed. We conclude that with the use of this model it is possible to induce a peripheral neuropathy in the Wistar rat which resembles that reported in humans and which can, therefore, be used to better understand the basic mechanism(s) of taxol toxicity and to evaluate protective strategies in an attempt to reduce it.
紫杉醇是一种具有抗肿瘤特性的天然提取物，已知对人类具有神经毒性。然而，其全身给药后的神经毒性在人类和动物的形态学水平上从未进行过详细研究。在本研究中，我们对雌性Wistar大鼠腹腔注射紫杉醇，并对其外周神经、背根神经节、脊髓神经根和脊髓进行了全面的神经生理学和形态学检查。在该实验模型中获得的结果表明，紫杉醇主要在外周神经中诱导病理变化，但在腹侧和背侧脊髓神经根以及脊髓背柱纤维中也存在。相反，背根神经节和脊髓神经元未受影响。全身给予紫杉醇引起的最显著变化是轴突内神经微管堆积。雪旺细胞显示出“激活”迹象，但未观察到明显的脱髓鞘现象。我们得出结论，使用该模型有可能在Wistar大鼠中诱导出类似于人类报道的周围神经病变，因此可用于更好地理解紫杉醇毒性的基本机制，并评估旨在降低其毒性的保护策略。
