Toxic effects of triethyldodecylammoniumbromide (TEA-C12) on myelinated nerve fibers and blood-nerve barrier in the mouse.
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.
Seitz
R J
RJ
Department of Neurology, University Hospital Düsseldorf, Federal Republic of Germany.
Lipfert
P
P
Willrich
A
A
Himmelmann
F
F
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005260:Female; D051379:Mice; D009413:Nerve Fibers, Myelinated / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D009431:Neural Conduction / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*
D000644:Quaternary Ammonium Compounds; C054210:N,N,N-triethyl-1-dodecylammonium