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Sensitive histological indicators of damage reveal treatment with supraphysiological levels of corticosterone and high dosages of kainic acid produce limited hippocampal damage in a strain of mice resistant to kainate neurotoxicity.

Benkovic-SA; Miller-DB
Toxicologist 2003 Mar; 72(S-1):73
The high levels of gIucocorticoids that accompany stress are believed to increase the sensitivity of the hippocampus to excitotoxic injury but this issue has received little examination utilizing mouse strains reported to be resistant to this type of neurotoxicity. We have previously utilized standard histological methods and GFAP ELISA to examine the interaction of supraphysiological levels of corticosterone and high doses of kainic acid on the integrity of the hippocampus in "kainate-resistant" C57BL/6J mice. No overt cell loss was evident in KA-treated mice but GFAP elevation indicated damage was present. Cort alone produced no damage, and was unable to exacerbate the injury produced by KA. Here, we used histological stains sensitive to damage (cupric-silver and Fluoro-Jade) to further characterize the interactions between supraphysiological levels of Cort and KA. C57BL/6J mice were implanted with 35 or 100 mg corticosterone pellets (68 mg/kg/d and 192 mg/kg/d respectively). After seven days, mice were injected with 35 mg/kg kainic acid and were allowed to recover for an additional seven days. These stains revealed moderate damage to hippocampal neurons caused by KA. In mice treated with Cort+KA, significant neuronal damage was observed in cortex and cerebellum; however, limited damage was seen in hippocampus. No damage profiles were observed in mice treated with Cort alone. These data suggest high physiological levels of corticosterone may attenuate hippocampal damage caused by certain neurotoxicants in mice.
Neurological-reactions; Neurotoxicity; Neurotoxic-effects; Neurotoxins; Stress; Psychological-stress; Laboratory-animals
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The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah