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Ultrastructural studies of the dying-back process. VI. Examination of nerve fibers undergoing giant axonal degeneration in organotypic culture.
J Neuropathol Exp Neurol. 1983 Mar; 42(2):153-65.JN

Abstract

Organotypic tissue cultures, composed of structurally and functionally coupled explants of mouse spinal cord, dorsal root ganglia, and striated muscle, have been used to create a model of the distal (dying-back) axonopathy found in animals and humans with aliphatic hexacarbon neuropathy. Mature explants were treated with 50-650 micrograms/ml of the following hexacarbons dissolved in nutrient fluid: n-hexane, 2-hexanol, 2,5-hexanediol, methyl n-butyl ketone, 5-hydroxy-2-hexanone, 2,5-hexanedione (all neurotoxic), or 2,4-hexanedione (a non-neurotoxic diketone). High concentrations (400-650 micrograms/ml) induced pancytotoxic damage and necrosis of tissue within days, while the lower doses (50-100 micrograms/ml) induced no pathological changes over a period of several weeks. Continuous exposure of explants to 245-325 micrograms/ml (2.8 mM) of the neurotoxic hexacarbons caused specific pathological changes to develop in distal nerve fibers after three to six weeks. Initial changes seen in distal, nonterminal regions of myelinated fibers included: nodal elongation, axonal swellings on proximal-side paranodes, and paranodal myelin retraction. Prolonged treatment was associated with Wallerian-like degeneration of distal nerve fibers. Denuded paranodal swellings in more proximal regions of affected myelinated fibers adopted a more-normal size and underwent remyelination; this occurred during and after the course of treatment. Remyelination by lateral extension from adjacent Schwann cells was documented in living and fixed tissue. The observations confirm the spatial-temporal evolution of hexacarbon distal axonopathy previously suggested from comparable studies in vivo.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6827287

Citation

Veronesi, B, et al. "Ultrastructural Studies of the Dying-back Process. VI. Examination of Nerve Fibers Undergoing Giant Axonal Degeneration in Organotypic Culture." Journal of Neuropathology and Experimental Neurology, vol. 42, no. 2, 1983, pp. 153-65.
Veronesi B, Peterson ER, Bornstein MB, et al. Ultrastructural studies of the dying-back process. VI. Examination of nerve fibers undergoing giant axonal degeneration in organotypic culture. J Neuropathol Exp Neurol. 1983;42(2):153-65.
Veronesi, B., Peterson, E. R., Bornstein, M. B., & Spencer, P. S. (1983). Ultrastructural studies of the dying-back process. VI. Examination of nerve fibers undergoing giant axonal degeneration in organotypic culture. Journal of Neuropathology and Experimental Neurology, 42(2), 153-65.
Veronesi B, et al. Ultrastructural Studies of the Dying-back Process. VI. Examination of Nerve Fibers Undergoing Giant Axonal Degeneration in Organotypic Culture. J Neuropathol Exp Neurol. 1983;42(2):153-65. PubMed PMID: 6827287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ultrastructural studies of the dying-back process. VI. Examination of nerve fibers undergoing giant axonal degeneration in organotypic culture. AU - Veronesi,B, AU - Peterson,E R, AU - Bornstein,M B, AU - Spencer,P S, PY - 1983/3/1/pubmed PY - 1983/3/1/medline PY - 1983/3/1/entrez SP - 153 EP - 65 JF - Journal of neuropathology and experimental neurology JO - J Neuropathol Exp Neurol VL - 42 IS - 2 N2 - Organotypic tissue cultures, composed of structurally and functionally coupled explants of mouse spinal cord, dorsal root ganglia, and striated muscle, have been used to create a model of the distal (dying-back) axonopathy found in animals and humans with aliphatic hexacarbon neuropathy. Mature explants were treated with 50-650 micrograms/ml of the following hexacarbons dissolved in nutrient fluid: n-hexane, 2-hexanol, 2,5-hexanediol, methyl n-butyl ketone, 5-hydroxy-2-hexanone, 2,5-hexanedione (all neurotoxic), or 2,4-hexanedione (a non-neurotoxic diketone). High concentrations (400-650 micrograms/ml) induced pancytotoxic damage and necrosis of tissue within days, while the lower doses (50-100 micrograms/ml) induced no pathological changes over a period of several weeks. Continuous exposure of explants to 245-325 micrograms/ml (2.8 mM) of the neurotoxic hexacarbons caused specific pathological changes to develop in distal nerve fibers after three to six weeks. Initial changes seen in distal, nonterminal regions of myelinated fibers included: nodal elongation, axonal swellings on proximal-side paranodes, and paranodal myelin retraction. Prolonged treatment was associated with Wallerian-like degeneration of distal nerve fibers. Denuded paranodal swellings in more proximal regions of affected myelinated fibers adopted a more-normal size and underwent remyelination; this occurred during and after the course of treatment. Remyelination by lateral extension from adjacent Schwann cells was documented in living and fixed tissue. The observations confirm the spatial-temporal evolution of hexacarbon distal axonopathy previously suggested from comparable studies in vivo. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/6827287/Ultrastructural_studies_of_the_dying_back_process__VI__Examination_of_nerve_fibers_undergoing_giant_axonal_degeneration_in_organotypic_culture_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=6827287.ui DB - PRIME DP - Unbound Medicine ER -