Walker J J, Phillips D E
Neurotoxicology. 1987 Spring;8(1):55-63.
This study examined the ultrastructural alterations in peripheral nerve of adult mouse following repeated sublethal exposures to endrin, a toxic chlorinated hydrocarbon which produces symptoms indicative of neuromuscular dysfunction. Male mice were given 20 daily ip injections of endrin in sesame oil (0.2 ml) in doses that increased from 1.5 mg/kg on days 0-3, to 2.0 mg/kg on days 4-11, and to 4.0 mg/kg on days 12-19. Controls were given the same intraperitoneal volume of sesame oil without endrin. Animals were sacrificed by glutaraldehyde perfusion after 4, 7, 14, and 20 days of exposure and 14 and 92 days postinjection and sciatic nerve tissue was prepared for electron microscopy. Myelinated nerve fibers, myelin and associated Schwann cells from endrin exposed animals appeared similar to those of controls and normal animals. Various morphological alterations were observed in many unmyelinated axons from endrin exposed animals. Such alterations included swelling, dissolution of microtubules and neurofilaments, the presence of unusual numbers of axoplasmic vesicles, both scattered and in packets, and less often, extreme vacuolation. In those Schwann cells associated with damaged axons the cytoplasm and the adaxonal space frequently contained vesicles, often in packets invaginating the axolemma. The results of this study indicate that repeated subacute doses of endrin can produce morphological alterations in unmyelinated peripheral nerve fibers and their associated Schwann cells without apparent damage to myelinated nerve fibers. The results are discussed relative to other studies producing similar nerve damage and to the potential mechanisms responsible for such damage.
本研究检测了成年小鼠反复亚致死剂量暴露于异狄氏剂(一种有毒的氯代烃,可产生神经肌肉功能障碍症状)后外周神经的超微结构变化。雄性小鼠每天腹腔注射20次异狄氏剂(溶于0.2 ml芝麻油),剂量从第0 - 3天的1.5 mg/kg增加到第4 - 11天的2.0 mg/kg,再到第12 - 19天的4.0 mg/kg。对照组注射相同体积不含异狄氏剂的芝麻油。在暴露4、7、14和20天以及注射后14和92天,通过戊二醛灌注处死动物,并制备坐骨神经组织用于电子显微镜检查。异狄氏剂暴露动物的有髓神经纤维、髓鞘和相关施万细胞看起来与对照组和正常动物相似。在异狄氏剂暴露动物的许多无髓轴突中观察到各种形态学改变。这些改变包括肿胀、微管和神经丝溶解、出现数量异常的轴浆小泡(既有散在的也有成簇的),较少见的还有极度空泡化。在与受损轴突相关的施万细胞中,细胞质和轴突旁间隙经常含有小泡,通常成簇并内陷至轴膜。本研究结果表明,反复亚急性剂量的异狄氏剂可导致无髓外周神经纤维及其相关施万细胞出现形态学改变,而对有髓神经纤维无明显损伤。结合其他产生类似神经损伤的研究以及造成此类损伤的潜在机制对结果进行了讨论。