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    Use of Selective Silver Impregnation of Neuronal Degeneration as a Biomarker for Assessing Organophosphorus-Induced Neuropathy in the Central Nervous System. A Review

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    Exposure to selected groups of organophosphorus compounds has been shown to result in neuronal degeneration in both avian and mammalian nervous systems. Previous investigators, using hematoxylin and eosin stains, concluded that the degeneration resulting from exposure to these compounds was restricted to peripheral nerves and to long fiber tracts of the spinal cord and lower brainstem. We re-examined the results of exposure to the organophosphorus compounds tri-o-tolyl phosphate, diisopropylphosphoro-fluoridate, and triphenyl phosphite using a variant of the Fink-Heimer silver impregnation method. This method selectively stains degenerating axons and axon terminals. Chickens, Japanese quail, rats, and mature and immature ferrets were used in these studies because of their differential clinical susceptibility to organophosphorus compounds. Our results indicate that exposure to each compound may result in a variable amount of degeneration within selected nuclei and tracts in the brain and spinal cord. The amount of degeneration seen in each instance corresponds well with the severity of the resultant clinical signs. In addition, the locus and severity of neuronal degeneration is dependent on the particular compound used, the species of animal exposed, and the age of the animal at the time of exposure.


    organophosphorus-induced delayed neurotoxicity, axonal degeneration, central nervous system, Fink-Heimer silver impregnation method, tri-, o, -tolyl phosphate, diisopropylphosphorofluoridate, triphenyl phosphite

    Author Information:

    Tanaka, D
    Professor, Michigan State University, East Lansing, MI

    Bursian, SJ
    Professor, Michigan State University, East Lansing, MI

    Committee/Subcommittee: E47.09

    DOI: 10.1520/STP12161S