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.

Post-traumatic endoneurial neovascularization and nerve regeneration: a morphometric study.

Neovascularization would be expected to play an important role in regeneration after nerve injury, but its mechanism is poorly understood. Quantitative investigations of endoneurial capillaries and myelinated fibers 5 and 15 mm distal to different types of nerve injury have therefore been performed. This study demonstrated that numbers of endoneurial capillaries were significantly increased at the 5 mm level 2, 4, 6 and 8 weeks after crush, transection and ischemic lesions, but not following permanent axotomy. Late neovascularization associated with delayed nerve regeneration was found following nerve ischemia. These results suggest that neovascularization following nerve injury is dependent on two variables, the degree of nerve regeneration and the severity of ischemia. Axonal outgrowth appears to be an important determinant of post-traumatic new capillary formation, while nerve ischemia causes both delayed neovascularization and nerve regeneration.

Myelopathy induced by lactic acid.

This study defines the conditions required to provoke myelopathic changes by dripping lactic acid onto the surgically exposed spinal cord of adult male rats. A severe necrotizing myelopathy was observed after 24 h, principally in the posterior half of the cord at the level of lactic acid (pH 1.8) application. A profound early effect on small blood vessel walls, appearing necrotic after 30 min to 2 h, was identified. Nerve fiber alterations (axonal stasis, granular axoplasm, axonal calcification, and vesicular myelin), identical to those appearing early in the myelopathies of trauma and calcium toxicity, were apparent. However, the pathogenesis of these alterations in this model remains unclear, because of the vascular events and the presumed alterations of calcium metabolism by the acid. Further studies are required to elucidate the precise mechanisms of these important reactions of myelinated axons to the injuries provoked by acid, calcium, and trauma.

Experimental study of vascularized nerve grafts: morphometric study of axonal regeneration of nerves transplanted into silicone tubes.

Rat sciatic nerves were used in a comparative study of vascularized and free (nonvascularized) nerve grafts transplanted into silicone tubes. A total of 39 sciatic nerves were used, 21 as vascularized nerve grafts and 18 as free nerve grafts. The rats were killed at intervals from the first to the 24th postoperative weeks, and biopsied sciatic nerves were processed for morphometric studies using a fiber caliber analyzer. There was a significant increase in the number of large myelinated axons (more than 5 mu) in the vascularized nerve graft models over those in the free nerve graft models at the distal ankle region. Furthermore, the diameters of myelinated axons in the vascularized nerve graft were larger than those in the free nerve graft at all specimen sites during all postoperative weeks. We suggest that the preservation of the vascular system in vascularized nerve grafts would decrease the likelihood of fibrosis and result in better regeneration of axons.