Fiori M G, Schiavinato A, Lini E, Nunzi M G
Postgraduate Program in Nerve Regeneration, Department of Orthopedics, University of Brescia School of Medicine, Italy.
Toxicol Pathol. 1995 May-Jun;23(3):248-55. doi: 10.1177/019262339502300302.
The lack of a suitable animal model for the peripheral neuropathy that often follows the systemic administration of the chemotherapeutic agent vincristine sulfate (VCR) has hampered the correlation between experimental and clinical patterns of this neuropathy. New Zealand rabbits have been recently found to develop, after iv injection of a VCR total dosage similar to that used in humans, a peripheral polyneuropathy characterized by electrophysiological changes that overlap those observed in the clinical setting. The present study was aimed at investigating the ultrastructural features of 3 different nerves (sural, peroneal, and medial gastrocnemius) in rabbits treated with 3 VCR doses that fall within the range (0.2-0.3 mg/kg i.v.) known to be efficacious chemotherapeutically and active neurotoxicologically. Regardless of the dose and the nerve under examination, histopathologic alterations appeared in the form of an overall loss of myelinated fibers, accompanied by successful attempts of regeneration and remyelination. Fibers undergoing Wallerian degeneration were characterized by an axoplasm, which was either watery-flocculent or divided in 2 or more regions as a consequence of ingrowing Schwann cell processes from the adaxonal surface. These ingrowths tended to isolate axoplasmic areas, retaining a fairly normal structure from other areas already crowded with altered organelles and cytoskeletal elements. In any event, neurofibrillary accumulations were rarely seen. These patterns are discussed with reference to those reported in the ultrastructural studies of human cases and confirm the suitability of rabbit as an animal model for VCR-induced peripheral neuropathy.
常用于全身给药的化疗药物硫酸长春新碱（VCR）引发的周围神经病变缺乏合适的动物模型，这阻碍了该神经病变实验模式与临床模式之间的关联研究。最近发现，给新西兰兔静脉注射与人类所用剂量相似的VCR总剂量后，会引发周围性多发性神经病变，其特征为电生理变化，与临床观察到的变化重叠。本研究旨在调查用3种VCR剂量治疗的兔的3种不同神经（腓肠神经、腓总神经和腓肠内侧肌神经）的超微结构特征，这3种剂量处于已知具有化疗疗效和神经毒理学活性的范围（静脉注射0.2 - 0.3 mg/kg）。无论剂量和所检查的神经如何，组织病理学改变均表现为有髓纤维全面丧失，并伴有成功的再生和髓鞘再生尝试。发生华勒氏变性的纤维的特征是轴浆，其要么呈水样絮状，要么由于施万细胞从轴突表面向内生长的过程而被分成两个或更多区域。这些向内生长的区域倾向于隔离轴浆区域，使其与其他已充满改变的细胞器和细胞骨架成分的区域保持相当正常的结构。无论如何，很少见到神经原纤维聚集。本文参照人类病例超微结构研究报告的模式对这些模式进行了讨论，并证实兔作为VCR诱导的周围神经病变动物模型的适用性。
