Neurotoxic effects of organic solvents on rapidly growing unmyelinated peripheral nerve axons of rat fetuses

2,5-己二酮（2,5- hd）是正己烷和甲基正丁基酮（MnBK）的常见代谢物，具有很高的神经毒性。周围神经系统（PNS）的早期退行性改变的特征是在远端受影响纤维的非末端区域的Ranvier淋巴结近端发生轴突肿胀和神经丝的积累。轴突转运速率的变化也有报道。大鼠胎儿的周围神经轴突正在快速生长，尚未形成髓鞘。在这个阶段，我们可以估计2,5- hd对生长轴突的直接影响，以及胎儿轴突与成人轴突对2,5- hd敏感性的差异。研究了三组怀孕大鼠。H组：从第12天至第16天暴露于2,5- hd 680 mg/kg。L组：从第12天至第19天暴露于2,5- hd 340 mg/kg。C组：对照组。首先对胎儿的坐骨神经和腓神经进行了形态学和形态计量学研究。神经轴突表现出特征性。一种是被雪旺细胞臂包围的群中轴突的融合，在h组中更为突出；另一种是轴突口径分布在直径更大的地方出现第二峰。H组腓神经轴突髓鞘形成延迟。各组间生殖指标无显著差异。观察2,5- hd暴露坝产仔鼠的行为，直至出生后第7周。H组和L组的生长速率在整个观察期内均受到抑制。出生后第41天，H组男性平均落地脚展宽较其他2组大，但在出生后第52天，差异无统计学意义。自发性运动活动未见变化。

2,5-Hexanedione(2,5-HD), a common metabolite of n-hexane and methyl n-butyl ketone (MnBK), has high neurotoxic potential. Early degenerative changes in the peripheral nervous system (PNS) are characterized by the development of axonal swellings with accumulated neurofilaments on the proximal side of nodes of Ranvier in distal, nonterminal regions of affected fibers. Changes in axonal transport rates were also reported. Axons of the peripheral nerves of rat fetuses are rapidly growing there length and are not yet myelinated. In this stage we can estimate the direct effects of 2,5-HD on growing axons and also the difference in sensitivity to 2,5-HD on fetal axons compared with the adult axons.Three groups of pregnant rats were studied. Group H : exposed to 2,5-HD 680 mg/kg from day 12 through day 16. Group L : exposed to 2,5-HD 340 mg/kg from day 12 through day 19. Group C : control. First the sciatic and peroneal nerves of the fetuses were studied morphologically and morphometrically. The nerve axons showed characterisitc features. One is a fusion of axons among the group surrounded by arms of a Schwann cell, which was more prominent in group H. Another is an appearance of the second peak at larger diameter in axon caliber distribution. The peroneal nerve axons of group H showed a delay in myelination. There were no differences in reproductive indices among the groups. The behavior of pups delivered from 2,5-HD exposed dams were observed until 7 th postnatal week. The growth rates were suppressed in group H and L through out the observation period. Mean landing foot splay of group H male was wider than those of other two in postnatal day 41 but the significance disappeared in postnatal day 52. No changes in spontaneous motor activities were observed.