Evidence for direct axonal toxicity in vincristine neuropathy
Evidence for direct axonal toxicity in vincristine neuropathy
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DOI：
10.1111/j.1529-8027.2006.0090.x
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发表时间：
2006-09-01
影响因子：
3.8
通讯作者：
Glass, Jonathan D.
中科院分区：
文献类型：
--
作者：
Silva, Angelica;Wang, Qingbo;Glass, Jonathan D.
关于导致远端轴突变性或‘死亡性’神经病的原发损伤的定位，存在着长期的争论。为了解决这个问题，我们在大鼠背根神经节(DRG)建立了长春新碱神经病的体外模型。DRG生长在隔室中，允许细胞体或轴突单独暴露于长春新碱。最初的剂量发现研究确定了长春新碱的剂量，当给药到细胞体或轴突间室时，对细胞死亡的影响不同。在0.05 mM的剂量下，暴露细胞体对轴突的生长没有影响，而在轴突间加入长春新碱可使轴突缩短，而不影响未暴露的姐妹轴突的生长。只有在生长的轴突尖端暴露时才能看到毒性。这些数据支持局部轴突毒性是长春新碱引起的远端轴突变性的原因。
There is a long-standing debate concerning the localization of the primary insult that results in distal axonal degeneration, or 'dying back' neuropathy. To address this question, we created an in vitro model of vincristine neuropathy in rat dorsal root ganglia (DRG). DRGs were grown in compartmentalized chambers, allowing for isolated exposure of the cell body or the axon to vincristine. Initial dose-finding studies identified a dose of vincristine that showed differential effects on cell death when delivered to either the cell body or the axonal compartment. At this dose of 0.05 mu M, exposure of the cell bodies had no effect on the growth of axons, whereas addition of vincristine to the axonal compartment caused axonal shortening without affecting the growth of unexposed 'sister' axons. Toxicity was seen only with exposure of the growing axonal tips. These data support localized axonal toxicity as a cause of distal axonal degeneration due to vincristine.