Vuorinen V S, Röyttä M
Department of Pathology, University of Turku, Finland.
Acta Neuropathol. 1990;79(6):653-62. doi: 10.1007/BF00294244.
The present investigation is a continuation of previous studies showing taxol-induced changes up to 4 weeks after a nerve crush. To evaluate the long-term cellular response to taxol, we have extended our morphological analysis of these changes in the taxol-treated nerve crush for up to 40 weeks after a single injection of taxol (PI). The results showed that Schwann cells exhibited a long-lasting and marked response when taxol was injected into the crushed peripheral nerve. During the first 2 months PI, taxol-induced giant axonal bulbs showed the formation of primitive nodes of Ranvier as a result of Schwann cell invaginations. The Schwann cell invaginations developed into nodes of Ranvier after 3-4 months PI together with the recovery of axonal bulbs. Ultrastructurally, cytoplasmic microtubule-related abnormalities were numerous up to 3 months PI and microtubules were seen to enclose degenerative myelin. Taxol-induced abnormalities in Schwann cells did not prevent their ability to produce myelin sheaths, although the accumulation of microtubules between myelin lamellae caused swellings of Schmidt-Lanterman incisures and paranodal myelin loops. Abnormal, extracellular collagen-like 5-nm-thin fibrils were noted closely associated with Schwann cells up to 10 weeks PI. Endoneurial cells, present as long rows without interconnections were noted in areas devoid of axonal sprouts up to 6-8 weeks PI. These cells showed marked cytoplasmic elongations and were covered by thickened basal lamina and contained several microtubule-related cytoplasmic structures, some of which have not been described previously. Taxol, when injected into crushed sciatic nerve induced a long-lasting response upon the Schwann cells with several ultrastructural abnormalities which correlate with changes in myelination and the development of nodes of Ranvier. These findings suggest that normal microtubule turnover is necessary for Schwann cells during nerve fiber regeneration.
本研究是先前研究的延续，先前研究表明，在神经挤压后长达4周的时间里，紫杉醇会引起变化。为了评估对紫杉醇的长期细胞反应，我们将对经紫杉醇处理的神经挤压后的这些变化的形态学分析延长至单次注射紫杉醇（PI）后40周。结果表明，当将紫杉醇注入挤压的周围神经时，雪旺细胞表现出持久且明显的反应。在PI后的前2个月，紫杉醇诱导的巨大轴突球由于雪旺细胞内陷而显示出原始郎飞结的形成。在PI后的3-4个月，随着轴突球的恢复，雪旺细胞内陷发展为郎飞结。在超微结构上，直至PI后3个月，与细胞质微管相关的异常情况很多，并且可见微管包裹着变性的髓磷脂。尽管微管在髓鞘板层之间的积累导致施密特-兰特尔曼切迹和结旁髓鞘环肿胀，但紫杉醇诱导的雪旺细胞异常并未阻止其产生髓鞘的能力。在PI后长达10周的时间里，发现异常的、细胞外的5纳米厚胶原样细纤维与雪旺细胞紧密相关。在PI后6-8周，在没有轴突发芽的区域发现了呈长排状且无相互连接的神经内膜细胞。这些细胞显示出明显的细胞质伸长，被增厚的基膜覆盖，并含有几种与微管相关的细胞质结构，其中一些结构以前未曾描述过。当将紫杉醇注入挤压的坐骨神经时，会对雪旺细胞产生持久的反应，并伴有几种超微结构异常，这些异常与髓鞘形成的变化和郎飞结的发育相关。这些发现表明，在神经纤维再生过程中，正常的微管周转对于雪旺细胞是必要的。
