title: Histopathologic changes in the brain, heart, and skeletal muscle of rhesus macaques, ten days after exposure to soman (an organophosphorus nerve agent).
abstract: OBJECTIVE
  Soman, an organophosphorus, anticholinergic, chemical warfare nerve agent, is studied at few research facilities, and there have been few pathologic studies of soman-exposed primates. We describe the brain, heart, and skeletal muscle lesions, review lesions described in literature, and discuss possible pharmacologic mechanisms for soman-induced neuron necrosis.
  
  
  METHODS
  In this retrospective, histopathologic study, records were obtained for 36 rhesus macaques (Macaca mulatta) that were euthanized 10 days after soman exposure, from a larger group of 103 monkeys that were exposed to soman and used for pharmacologic and lethality studies.
  
  
  RESULTS
  Brain lesions were seen in 9 of 15 animals that convulsed and in only 1 of 21 that did not convulse. The brain lesions in our primates were limited to the hippocampus, amygdala, and thalamus (of one animal), and consisted of neuron necrosis and dropout, spongiosis, gliosis, astrocytosis, and vascularization. Heart lesions consisted of myocardial degeneration and necrosis. Three animals had brain and heart lesions, 7 had brain lesions only, and 3 had heart lesions only. Skeletal muscle lesions, although minimal to mild, were in most of the animals, whether they had convulsed, but most had muscular tremors. These lesions were in the biceps brachii (11 of 22 monkeys), anterior tibialis (8/22), biceps femoris (7/22), flexor carpi radialis (5/22), gastrocnemius (3/22), and diaphragm (1/22). The limited literature on soman lesions in primate brain and heart, and the limited information on skeletal muscle lesions, is reviewed.
  
  
  CONCLUSIONS
  Brain lesions were not as wide-spread as reported in other studies of primates and rodents, and were significantly associated with convulsions. Unlike other studies using rodents, we observed poor correlation between heart and brain lesions; thus, a single hypothesis to explain the pathogenesis for the brain and heart lesions may be difficult to establish.
authors.affiliation: US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA.
authors.forename: J O
authors.initials: JO
authors.lastname: Britt
authors.forename: J L
authors.initials: JL
authors.lastname: Martin
authors.forename: C V
authors.initials: CV
authors.lastname: Okerberg
authors.forename: E J
authors.initials: EJ
authors.lastname: Dick
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002619:Chemical Warfare Agents / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D006321:Heart / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009943:Organophosphorus Compounds / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D012999:Soman / Q000633:toxicity*; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D005904:Glial Fibrillary Acidic Protein; D009943:Organophosphorus Compounds; D012999:Soman