tellurium and Nerve-Degeneration

Neuropathy in animals is either genetically determined or is provoked by chemical compounds or physical injury. Diabetes in mice and rats may be spontaneous or induced, but a true copy of diabetic neuropathy in man is not yet available. Painful neuropathy occurs after nerve constriction or neuroma formation. A mouse mutant with delayed Wallerian degeneration demonstrates the pivotal role of this process for the regeneration of injured axons. Surprisingly, the neurotoxic effect of cisplatin which is severe in cancer patients has not yet unambiguously been reproduced in animals. Genetically determined diseases in mutants or transgenic animals may affect the myelination of peripheral axons. 'Trembler mice' are deficient in myelin and possibly correspond to CMT IA in man. The relation of sensory neuronopathies in mice, rats and dogs to human diseases is not yet clear. Motor neuronopathies in experimental animals have attracted much interest, because the recent discovery of motoneuronotrophic factors has raised high hopes. Most of the mutants described have not been appropriately studied, and the mouse mutant 'motoneurone disease' (mnd) eventually was found to have Batten's disease. None of the few more thoroughly studied models is probably a copy of human disease, although they may none the less help to test new therapies.

Topics: Animals; Antineoplastic Agents; Cisplatin; Diabetic Neuropathies; Dogs; Hereditary Sensory and Autonomic Neuropathies; Humans; Male; Mice; Nerve Degeneration; Nerve Regeneration; Peripheral Nerves; Radioisotopes; Rats; Tellurium

In this study, we evaluated the effects of three simple organochalcogenides (diphenyl diselenide, diphenyl ditelluride and diphenyl telluride) and ebselen on the glutamate-driven 45Ca2+ influx into chick embryonic retinal cells, as well as their effects on the excitotoxic injury in retina cells. None of the compounds tested interfered with basal 45Ca2+ uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven 45Ca2+ influx. Diphenyl telluride (100-400 microM) decreased and ebselen (100-400 microM) completely blocked the glutamate-driven 45Ca2+ influx (P < 0.01) into chick retinal explants. The assessment of neural injury was made spectrophotometrically by quantification of cellularly reduced MTT (3(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) 24 h after the beginning of glutamate exposure (8 h). Ebselen had no effects on retinal MTT reduction when co-incubated with glutamate for 8 h. However, when ebselen (100 and 400 microM) was co-incubated for 8 h with glutamate and remained in the incubation media until MTT evaluation (24 h after the beginning of incubation), it protected retinal cells against the decrease in MTT reduction induced by glutamate. These data indicate that besides its capacity of interacting with Ca2+ channels, other mechanisms are involved in the neuroprotection afforded by ebselen in this work, possibly its antioxidant properties.

Topics: Animals; Azoles; Benzene Derivatives; Calcium; Calcium Channels; Chalcogens; Chick Embryo; Dose-Response Relationship, Drug; Glutamic Acid; Isoindoles; Nerve Degeneration; Neurons; Neuroprotective Agents; Neurotoxins; Organometallic Compounds; Organoselenium Compounds; Retina; Tellurium; Tetrazolium Salts; Thiazoles

The synthesis and endoneurial distribution of apolipoproteins in response to myelin degradation was elucidated morphologically and biochemically in rodent models of segmental demyelination. At the onset of acute demyelination induced by tellurium (Te) poisoning, macrophages infiltrated the endoneurium and then began to express cytoplasmic immunoreactivity for apolipoprotein E (apo E). When demyelinating nerve slices were incubated with S35-methionine, radiolabeled apo E was released, showing that apo E was actively synthesized by the macrophages. Macrophages secreted apo E into the endoneurial spaces, leading to dense endoneurial accumulations. Other apolipoproteins (apo A1 and albumin) were not synthesized in the endoneurium, but they entered edematous nerves, presumably through an early breakdown in the blood-nerve barrier. During the phagocytosis of myelin, plasma-derived apolipoproteins accumulated within some of the macrophages. In chronic demyelination caused by lead poisoning, the cellular and extracellular distribution of apolipoproteins was similar to Te neuropathy; the amount of apo E accumulation and the macrophage density were proportional to the prevalence of active demyelination in teased fibers. Similar patterns of endoneurial apo E were present in an inherited form of demyelination in the twitcher mouse, after antibody-mediated demyelination, and in demyelination secondary to axonal degeneration. Human sural nerve biopsies had patterns of apolipoprotein E antigenicity that were comparable to the rodent models. We conclude that secretion of apo E by infiltrating macrophages is a generalized response to demyelination, and that endoneurial edema leads to the accumulation of certain plasma apolipoproteins within macrophages. These data suggest that endoneurial apolipoproteins and macrophages might mediate important functions in patients recovering from primary and secondary demyelination.

Topics: Animals; Apolipoproteins E; Demyelinating Diseases; Macrophages; Male; Nerve Degeneration; Nervous System; Nervous System Diseases; Rats; Sciatic Nerve; Tellurium

Topics: Animals; Brain Diseases; Cell Membrane; Cerebral Cortex; Cytoplasmic Granules; Disease Models, Animal; Lipidoses; Microscopy, Electron; Mitochondria; Nerve Degeneration; Pigments, Biological; Rats; Spectrophotometry, Atomic; Tellurium

Topics: Animals; Axons; Cytoplasm; Demyelinating Diseases; Inclusion Bodies; Macrophages; Microscopy, Electron; Myelin Sheath; Nerve Degeneration; Neurilemma; Rats; Rats, Inbred Strains; Schwann Cells; Sciatic Nerve; Tellurium; Time Factors