Axonal Atrophy Is a Specific Component of 2,5-Hexanedione Peripheral Neuropathy

E. J. Lehning, K. S. Dyer, B. S. Jortner, Richard M. LoPachin

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

To assess the relevance of previously identified axonal atrophy to hexanedione neuropathy, the present study quantitated fiber size in peripheral nerve of rats intoxicated with 2,5-hexanedione (HD) by either oral ingestion (0.4% in drinking water) or ip injection (0.4 g/kg/day). Prior to the appearance of neurobehavioral deficits, rats exposed to oral HD (77 days) exhibited axonal atrophy in proximal sciatic nerve and giant axonal swellings in distal tibial nerve. As oral-treated rats progressed to moderate (86 days) and severe (103 days) hindlimb weakness, both nerve regions contained a mixed population of atrophied and swollen axons. Rats injected with HD ip were sampled at behavioral endpoints that matched those of oral HD-treated rats. In sciatic and tibial nerves from rats treated ip, reductions in the axon area were similar to oral exposure. However, ip treatment did not produce giant axonal swellings in either nerve. Thus, although both routes of administration caused equivalent behavioral neurotoxicity, the expression of axonal swellings was route-dependent. This suggests that the production of swellings depends upon the HD exposure pattern. In contrast, axonal atrophy was prevalent in both nerve regions sampled and developed in parallel with behavioral deficits. In addition, atrophy was expressed regardless of the intoxication route which indicates that atrophy can occur independent of axonal swellings. Together, these attributes suggest that atrophy is a specific component of HD neurotoxicity.

Original languageEnglish (US)
Pages (from-to)58-66
Number of pages9
JournalToxicology and Applied Pharmacology
Volume135
Issue number1
DOIs
StatePublished - Nov 1995

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Peripheral Nervous System Diseases
Atrophy
Rats
Swelling
Tibial Nerve
Sciatic Nerve
Axons
Hindlimb
Peripheral Nerves
Drinking Water
2,5-hexanedione
Eating
Injections
Fibers
Population

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Axonal Atrophy Is a Specific Component of 2,5-Hexanedione Peripheral Neuropathy. / Lehning, E. J.; Dyer, K. S.; Jortner, B. S.; LoPachin, Richard M.

In: Toxicology and Applied Pharmacology, Vol. 135, No. 1, 11.1995, p. 58-66.

Research output: Contribution to journalArticle

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