Seitz R J, Lipfert P, Willrich A, Himmelmann F
Department of Neurology, University Hospital Düsseldorf, Federal Republic of Germany.
Exp Brain Res. 1989;74(2):293-302. doi: 10.1007/BF00248862.
The blocking effect of triethyldodecylammoniumbromide (TEA-C12), applied locally to the sciatic nerve, was studied in 28 adult BDF1 mice. Clinical parameters, electrophysiological recordings of muscle action potentials evoked by stimulation at the sciatic notch, and morphological aspects are presented. Our results show that both the minimal blocking concentration and half the minimal blocking concentration induce flaccid paresis of the treated hind-limb. There was a complete, long-lasting nerve conduction block due to Wallerian degeneration of the myelinated nerve fibers. In contrast, pain sensation was abolished only on day 4 after application of the minimal blocking concentration, but was preserved during the rest of the time that nerve conduction block was observed. This correspond to the electron microscopic finding of preservation of unmyelinated nerve fibers. Recovery of nerve conduction was characterized electrophysiologically by occurrence of minute polyphasic regeneration potentials between day 18 and 21, clinically by advanced restitution of muscle force on day 64, and morphologically by nerve regeneration. TEA-C12 also induced a disturbance of the blood-nerve barrier, demonstrated using an intraperitoneally administered biotinylated IgG tracer in the endoneurial space. The morphological features of the acute axonal changes of the myelinated nerve fibers including the degeneration of the axonal mitochondria suggest that the neurotoxic effect of TEA-C12 is possibly mediated by interference with the axonal energy supply. The selective affection of myelinated nerve fibers separates TEA-C12 from other neurotoxins that induce changes of the axonal microorganelles or complete Wallerian degeneration of myelinated and unmyelinated nerve fibers. The selectivity for myelinated nerve fibers and the supposed pathogenetic mechanism exhibit some similarities with the human polyneuropathy caused by acute arsenic acid intoxication.
在28只成年BDF1小鼠中研究了局部应用于坐骨神经的三乙基十二烷基溴化铵（TEA-C12）的阻断作用。呈现了临床参数、刺激坐骨切迹诱发的肌肉动作电位的电生理记录以及形态学方面的情况。我们的结果表明，最小阻断浓度和最小阻断浓度的一半均会导致受试后肢出现弛缓性麻痹。由于有髓神经纤维的华勒氏变性，出现了完全、持久的神经传导阻滞。相比之下，仅在应用最小阻断浓度后的第4天痛觉消失，但在观察到神经传导阻滞的其余时间内痛觉得以保留。这与电子显微镜下未髓鞘化神经纤维得以保留的发现相符。神经传导的恢复在电生理上表现为在第18天至21天出现微小的多相再生电位，临床上表现为在第64天肌肉力量的显著恢复，形态学上表现为神经再生。TEA-C12还导致血神经屏障紊乱，这是通过在神经内膜间隙腹腔注射生物素化IgG示踪剂来证明的。有髓神经纤维急性轴突变化的形态学特征包括轴突线粒体的变性，这表明TEA-C12的神经毒性作用可能是通过干扰轴突能量供应介导的。有髓神经纤维的选择性损伤使TEA-C12与其他诱导轴突微细胞器变化或有髓和无髓神经纤维完全华勒氏变性的神经毒素区分开来。对有髓神经纤维的选择性以及推测的发病机制与急性砷酸中毒引起的人类多发性神经病有一些相似之处。
