Advertisement

Pathology of Experimental Nerve Agent Poisoning

  • Charles G. McLeodJr.
  • Henry G. Wall

Abstract

Historically, organophosphorus toxicity has been most frequently associated with delayed peripheral neuropathies (Spencer, 1978; Lotti, 1984). Studies of accidental human exposures to these compounds and numerous animal experiments have shown that the symptomatic and morphologic effects of these toxic substances are related to distal disruptions of motor nerve tracts. The best described of these substances are triorthocresylphosphate (TOCP) and certain of the agricultural insecticides. More recently several investigators have defined an entirely different syndrome caused by two of the organophosphorus chemical warfare agents (Petras, 1981; Lemercier, 1983; McLeod, 1984; Samson, 1984; Martin, 1985; Singer, 1985; Singer, 1985). These highly toxic “nerve agents” are potent acetylcholinesterase inhibitors that have been found to induce severe brain pathology in several experimental animal models. The purpose of this review is to describe the light and electron microscopic pathological changes that are caused by these agents and to propose several possible etiologic mechanisms based on comparisons of observed lesions with other forms of central nervous system injury.

Keywords

Brain Pathology Central Nervous System Injury Nerve Agent Army Medical Research Aberdeen Prove Ground 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boskovic, B., 1981, The treatment of soman poisoning and its perspectives, Fund. & Appl. Tox., 1: 203–213.CrossRefGoogle Scholar
  2. Brown, A. W., Brierly, J. B., 1972, Anoxic-ischaemic cell change in rat brain. Light microscopic and fine structural observations. J. Neurol. Sci., 16: 59–84.PubMedCrossRefGoogle Scholar
  3. Garcia, J. H., Lossinsky, A. S., Kauffman, F. C., and Conger, K. A., 1978, Neuronal ischemic injury: light microscopy, ultrastructure and biochemistry, Acta. Neuropathol. (Berl), 43: 85–95.CrossRefGoogle Scholar
  4. Harris, C., Koon, W., Crook, J. W., Christensen, M., and Oberst, F. W., 1953, Do pathological lesions develop in dogs repeatedly exposed to low doses of GB vapor? DTIC Tech. Report #AD3399, Chemical Corps, Medical Labs, Army Chemical Center, Aberdeen Proving Ground, Maryland.Google Scholar
  5. Lemercier, G., Carpenter, P., Sentenac-Romanou, H., and Morelis, P., 1983, Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound, Acta. Neuropathol. (Berl), 61: 123–129.CrossRefGoogle Scholar
  6. Lohs, Kh., 1975, Delayed toxic effects of chemical warfare agents, Stockholm: Almqvist & Wiksell, International Peace Research Institute, c1975.Google Scholar
  7. Lotti, M., Becker, C. E., and Aminoff, M. J., 1984, Organophosphate polyneuropathy: Pathogenesis and prevention, Neurol. 34, 658–662.CrossRefGoogle Scholar
  8. Martin, L. J., Doebler, J. A., Shih, T. M., and Anthony, A., 1985, Protective effect of diazepam pretreatment on soman-induced brain lesion formation, Brain Res. 325, 287–289.PubMedCrossRefGoogle Scholar
  9. McLeod, C. G., Jr., Singer, A. W., and Harrington, D. G., 1984, Acute neuropathology in soman poisoned rats, Neurotoxicology, 5: 53–58.PubMedGoogle Scholar
  10. McLeod, C. G., Jr., 1985, Pathology of nerve agents: Perspectives on medical management, Accepted for publication, Fund. & Appl. Toxicol.Google Scholar
  11. Petras, J. M., 1981, Soman neurotoxicity, Fund. & Appl. Toxicol., 1: 242.CrossRefGoogle Scholar
  12. Petras, J. M., 1984, Brain pathology induced by organophosphate poisoning with the nerve agent soman, U. S. Army Medical Research Development Command 4th Annual Chemical Defense Bioscience Review.Google Scholar
  13. Samson, F. E., Pazdernik, T. L., Cross, R. S., Giesler, M. P., Mewes, K., Nelson, S. R., and McDonough, J. H., 1984, Soman induced changes in brain regional glucose use, Fund. Appl. Toxicol., 4: 173–183.CrossRefGoogle Scholar
  14. Singer, A. W., 1984, Effect of Valium and atropine on mortality and pathology in guinea pigs exposed to soman, U. S. Army Medical Research Development Command 4th Annual Chemical Defense Bioscience Review.Google Scholar
  15. Singer, A. W. and McLeod, C. G., Jr., 1985, Effect of diazepam on soman induced neuropathology, Submitted for publication, Neurotoxicology.Google Scholar
  16. Singer, A. W., Graham, J. S., and McLeod, C. G., Jr., 1985, Acute neuropathology and cardiomyopathy in soman and sarin poisoned rats, Submitted for publication, Tox Letters.Google Scholar
  17. Spencer, P. S., Schaumburg, H. H., 1978, Distal axonopathy: One common type of neurotoxic lesion, Environ. Health Perspect. 26: 97–105.PubMedCrossRefGoogle Scholar
  18. Spencer, P. S., Albuquerque, E. X., Dettbarn, W. D., Drachman, D. B., Generoso, W. M., Karczmar, A. G., Koelle, G., and Standaert, F. S., 1982, Chapters 1 (Introduction) and 2 (Anticholinesterases), In: “Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents,” Vol 1, Anticholinesterases and Anticholinergics., Nat. Acad, Press, Washington D.C.Google Scholar
  19. Thorton, K. R., and Brigden, E. G., 1962, Morphological changes in the brain of guinea pigs following VX poisoning, Suffield Technical Paper No. 230.Google Scholar
  20. Trump, B. F., McDowell, E. M., and Arstila, A. U., Cellular reaction to injury, In: “Principles of Pathobiology.,” ed. LaVia.Google Scholar
  21. Vojvodic, V., 1981, Toxicology of war gases, Belgrade Military Publishing House, Inst for Mil Med Inform and Documentation, Biblioteka Pravila: udzbenici., 5: 198–226.Google Scholar
  22. Wall, H. G., McLeod, C. G., Jr., Hutchison, L. S., and Shutz, M., 1985, Development of brain lesions in rats surviving after experiencing soman induced convulsions: Light and electron microscopy, U. S. Army Medical Research Development Command 5th Annual Chemical Defense Bioscience Review.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Charles G. McLeodJr.
    • 1
  • Henry G. Wall
    • 1
  1. 1.U. S. Army Medical Research Institute of Chemical DefenseAberdeen Proving GroundUSA

Personalised recommendations