Summary
The pattern of recovery of myelinated axons in the posterior tibial nerve after crushing was studied in rats chronically intoxicated with 2,5-hexanedione. It was given for 2 weeks before curshing (200 mg/kg i.p. 5 times a week) or additionally for two further weeks after the nerve crush. Two animals were examined from each group at approximately, 1, 2, 3, 4, and 8 weeks later.
Return of function in poisoned animals was slower than in the controls. The numbers of regenerating myelinated fibres was severely reduced in poisoned animals, up to 4 weeks later, but by 8 weeks the numbers equalled those in the control nerves. Marked impairment of initiation of neurite outgrowth was found, but once begun, axonal growth was comparable to controls and myelination occurred normally. Above the crush for 10 mm, filament-filled axonal swellings were found in poisoned animals accompanied by varying amounts of retrograde axonal degeneration. These findings are discussed in relation to the role of normal neurofilaments in axonal growth and the effects of probably cross-linking of these by 2,5-hexanedione on regnerating neurites.
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References
Aitken JT, Sharman M, Young JZ (1947) Maturation of regenerating nerve fibres with various peripheral connections. J Anat 81: 1–22
Allen N, Mendell JR, Billmaier PT, Fontaine RE, O'Neill J (1975) Toxic polyneuropathy due to methyl n-butyl, ketone. An industrial outbreak. Arch Neurol 32:209–222
Cangiano A, Lutzemberger J, Rizzuto N, Simonati A, Rossi A, Toschi G (1981) Neurotoxic effects of 2,5-hexanedione in rats: early morphological and functional changes in nerve fibres and neuromuscular junctions. Neurotoxicology 2:25–32
Cavanagh JB (1982) The pattern of recovery of axons in the nervous system of rats following 2,5-hexanediol intoxication: a question of rheology? Neuropathol Appl Neurobiol 8:19–34
Cavanagh JB, Gysbers MF (1981) “Dying back” above a nerve ligature produced by acrylamide. Acta Neuropathol (Berl) 51:169–177
Cavanagh JB, Gysbers MF (1981) Ultrastructural, changes in axons caused by acrylamide above a nerve ligature. Neuropathol Appl Neurobiol 7:315–326
Cianchetti C, Abbritti G, Perticoni G, siracusa A, Curradi F (1976) Toxic polyneuropathies of shoe-industry workers. A stydy of 122 cases. J Neurol Neurosurg Psychiatry 39:1151–1161
Couri D, Abdel-Rahman MS, Hetland LB (1976) Biotranstormation of hexane and methyl n-butyl ketone. Toxicol Appl Pharmacol 37:124–125
Di Vincenzo GD, Kaplan CJ, Dedinas J (1976) Characterisation of the metabolites of methyl n-butyl, ketone, methyl iso-butyl ketone and methyl ethyl ketone in guinea pig serum and their clearance. Toxicol Appl Pharmacol 36:511–522
Forman DS, Berenberg RA (1978) Regeneration of motor axons in the rat sciatic nerve studied by labelling with axonally transported radioactive proteins. Brain Res 156:213–225
Friede RL, Martinez AJ (1970) Analysis of the process of sheath expansion in swollen nerve fibres. Brain Res 19:165–182
Friede RL, Miyagishi T (1972) Adjustment of the myelin sheath to changes in axon caliber. Anat. Rec 172:1–14
Graham D (1980) Hexane neuropathy: a proposal for pathogenesis of a hazard of occupational exposure and solvent abuse. Chem-Biol Interact 32:335–345
Griffin JW, Price DL, Spencer PS (1977) Fast axonal transport through giant axonal swellings in hexacarbon neuropathy. J Neuropathol Exp Neurol 36:603 [Abstract]
Guttman E, Guttman L, Medawar P Young JZ (1942) The rate of regeneration of nerve. J Exp Biol 19:14–44
Hoffman PN, Lasek RJ (1980) Axonal transport of the cytoskeleton in regenerating motor neurons: constancy and change. Brain Res 202:317–333
Jones JB, Cavanagh JB (1983) Distortions of the nodes of Ranvier from axonal distension by filamentous masses in hexacarbon intoxication. J Neurocytol 12: (in press)
Korobkin R, Asbury AK, Summer AJ, Nielsen L (1975) Glue-sniffing neuropathy. Arch Neurol 32:158–162
Lasek RJ (1981) The dynamic ordering of neuronal cytoskeleton. In: Lasek RJ, Shelanski ML (eds) Cytoskeleton and the architecture of nervous system. Neurosci Res Program Bull 19: 7–31
Lasek, RJ, Hoffman PN (1976) The neuronal cytoskeleton, axonal transport and axonal growth. In: Goldman RD, Pollard T, Rosenbaum J (eds) Cell motility, book C. Microtubules and related proteins. Cold Spring Harbor Lab, New York, pp 1021–1049
Lubinska L (1955) Region of transition between preserved and regenerated parts of myclinated nerve fibres. J Comp Neurol 113:315–335
Martinez AJ, Friede RL (1970) Accumulation of axoplasmic organelles in swollen nerve fibres. Brain Res 19:183–198
Mendell JR, Sahenk Z, Saida K, Weiss HS, Savage R, Couri D (1977) Alterations of fast axoplasmic transport in experimental methyl n-butylketone neuropathy. Brain Res 133:107–118
Politis MJ, Pellegrino RG, Spencer PS (1980) Ultrastructural studies of the dying-back, process. V. Axonal neurofilaments accumulate at sites of 2,5-hexanedione application: evidence for nerve fibre dysfunction in experimental hexacarbon neuropathy. J neurocytol 9:505–516
Powell HC, Koch T, Garrett R, Lampert PW (1978) Schwann cell abnormalities in 2,5-hexanedione neuropathy. J Neurocytol 7:517–528
Rizzuto N, De Grandis D, Di Trapani G, Pasinato E (1980) n-Hexane polyneuropathy. An occupational disease of shoemakers. Eur Neurol 19:308–315
Rizzuto N, Terzian H, Galiazzo-Rizzuto S (1977) Toxic polyneuropathies in Italy due to leather cement poisoning in shoe industries. A light and electron microscopic study. J Neurol Sci 31:343–354
Rossi A, Simonati A, Rizzuto N, Toschi G (1982) Neurotoxic action of 2,5 hexanedione on the autonomic nervous system: ultrastructural and functional alterations in the rat sympathetic superior cervical ganglion. Brain Res 243:373–377
Simonati A, Rizzuto N, Galiazzo-Rizzuto S, Cavanagh JB (1981) Regeneration of peripheral nerve fibre after crush in 2,5 hexanedione intoxication. Neurosci Lett [Suppl] VII:300a
Sobue I, Iida M, Yamamura Y, Takayanagui T (1976) n-Hexane polyneuropathy. Int J Neurol 11:317–330
Spencer PS, Schaumburg HH (1975) Experimental neuropathy produced by 2,5-hexanedione — a major metabolite of the neurotoxic industrial solvent methyl n-butyl ketone. J Neurol Neurosurg Psychiatry 8:771–775
Spencer PS, Schaumburg HH (1977) Ultrastructural studies of the dying-back process. II. The evolution of experimental peripheral giant axonal degeneration. J Neuropathol Exp Neurol 36:276–299
Standring SM, Gregson NA (1982) The effects of 2,5-hexanedione on remyelination in the peripheral nervous system of the mouse. J Neuropathol Exp Neurol 41:642–651
Towfighi J, Gonatas NK, Pleasure D, Cooper HS, McCree L (1976) Glue sniffer's neuropathy. Neurology 26:238–243
Yamada S (1967) Intoxication polyneuritis in the workers exposed to n-hexane. Jpn J Ind Health 9:651–659
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Partly supported by CNR Grant No. CT 81.00336.04
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Simonati, A., Rizzuto, N. & Cavanagh, J.B. The effects of 2,5-hexanedione on axonal regeneration after nerve crush in the rat. Acta Neuropathol 59, 216–224 (1983). https://doi.org/10.1007/BF00703206
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DOI: https://doi.org/10.1007/BF00703206