Pathology of Experimental Nerve Agent Poisoning
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.
KeywordsBrain Pathology Central Nervous System Injury Nerve Agent Army Medical Research Aberdeen Prove Ground
Unable to display preview. Download preview PDF.
- 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
- Lohs, Kh., 1975, Delayed toxic effects of chemical warfare agents, Stockholm: Almqvist & Wiksell, International Peace Research Institute, c1975.Google Scholar
- McLeod, C. G., Jr., 1985, Pathology of nerve agents: Perspectives on medical management, Accepted for publication, Fund. & Appl. Toxicol.Google Scholar
- 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
- 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
- Singer, A. W. and McLeod, C. G., Jr., 1985, Effect of diazepam on soman induced neuropathology, Submitted for publication, Neurotoxicology.Google Scholar
- 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
- 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
- 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
- Trump, B. F., McDowell, E. M., and Arstila, A. U., Cellular reaction to injury, In: “Principles of Pathobiology.,” ed. LaVia.Google Scholar
- 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
- 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