γ-Diketone central neuropathy: Quantitative morphometric analysis of axons in rat spinal cord white matter regions and nerve roots

Richard M. LoPachin, Bernard S. Jortner, Maria L. Reid, Soma Das

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A quantitative analytical method was used to measure myelinated axon morphometric parameters (e.g., axon area, ratio of axon area/fiber area, and index of circularity) in rat nervous tissue during intoxication with 2,5-hexanedione (HD). Parameters were assessed in nerve roots (dorsal and ventral) and in ascending (gracile fasciculus and spinocerebellar tract) and descending (corticospinal and rubrospinal tracts) spinal cord white matter tracts (L4-L5) of rats intoxicated with HD at two different daily dose-rates (175 or 400 mg HD/kg/day, gavage). For each dose-rate, tissue was sampled at four neurological endpoints: unaffected, slight, moderate, and severe toxicity, as determined by gait analysis and measurements of grip strength. Results indicate that, regardless of the HD dose-rate, axon atrophy (reduced axon area) was a widespread, abundant effect that developed in concert with neurological deficits. The atrophy response occurred contemporaneously in both ascending and descending spinal tracts, which suggests that loss of caliber developed simultaneously along the proximodistal axon axis. In contrast, swollen axons were a numerically small component and were present in nerve roots and spinal tracts only during subchronic intoxication at the lower HD dose-rate (i.e., 175 mg/kg/day). Intoxication at the higher dose-rate (400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. These observations in conjunction with our previous studies of HD-induced peripheral neuropathy (Toxicol. Appl. Pharmacol. 135 (1995) 58; and Toxicol. Appl. Pharmacol. 165 (2000) 127) indicate that axon atrophy, and not axonal swelling, is a primary neuropathic phenomenon.

Original languageEnglish (US)
Pages (from-to)29-46
Number of pages18
JournalToxicology and Applied Pharmacology
Volume193
Issue number1
DOIs
StatePublished - Nov 15 2003

Fingerprint

Axons
Rats
Spinal Cord
Chemical analysis
Spinal Nerve Roots
Atrophy
Swelling
Spinocerebellar Tracts
Tissue
Gait analysis
Nerve Tissue
Pyramidal Tracts
White Matter
Hand Strength
Peripheral Nervous System Diseases
Gait
Toxicity
Fibers

Keywords

  • γ-Diketone neuropathy
  • 2,5-Hexanedione
  • Axon atrophy
  • Axon swellings
  • Distal axonopathy

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

γ-Diketone central neuropathy : Quantitative morphometric analysis of axons in rat spinal cord white matter regions and nerve roots. / LoPachin, Richard M.; Jortner, Bernard S.; Reid, Maria L.; Das, Soma.

In: Toxicology and Applied Pharmacology, Vol. 193, No. 1, 15.11.2003, p. 29-46.

Research output: Contribution to journalArticle

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