Immunohistopathology in the Guinea Pig Following Chronic Low-Level Exposure to Chemical Warfare Agents
Technical rept., May 2003-Apr 2005
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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Guinea pigs exposed repeatedly to low levels of chemical warfare nerve agents exhibit behavioral changes, but no histopathological changes using traditional hematoxylineosin staining. To observe mild cytopathology, this study utilizes more sensitive methodologies of MAP-2 immunohistochemistry and Fluoro-Jade histofluorescence. Diet-unrestricted Male Hartley guinea pigs were exposed to 0.4 and 0.5 LD50 VX, soman, or sarin for 2 weeks, three weeks, or four weeks. A second group of diet-restricted guinea pigs was injected with 0.1, 0.2, or 0.4 LD50 VX for 1 week, 2 weeks, or 2 weeks followed by 1 week of recovery. Animals were euthanized with sodium pentobarbital and perfused with formalin. Brain sections were stained with MAP-2 and Fluoro-Jade. No changes in MAP-2 or Fluoro- Jade labeling were observed in diet-unrestricted animals. Diet-restricted animals exposed to 0.1 and 0.2 LD50 VX showed no alterations in MAP-2. Exposure to 0.4 LD50 VX resulted in increased MAP-2, however increased MAP-2 was not observed in 0.4 LD50 VX groups allowed to recover for 1 week. Results suggest that increased MAP-2 immunoreactivity could be due to an acute phase of increased neuronal activity as part of compensatory and repair mechanisms. Diet restriction may increase resistance of neurons to irreversible damage and facilitate recovery.
- Chemical, Biological and Radiological Warfare