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Neurotoxicology. 2009 Nov;30(6):965-76. doi: 10.1016/j.neuro.2009.07.005. Epub 2009 Jul 16.

Protracted exposure to supraphysiological levels of corticosterone does not cause neuronal loss or damage and protects against kainic acid-induced neurotoxicity in the hippocampus of C57BL/6J mice.

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1
Toxicology and Molecular Biology Branch, Centers for Disease Control and Prevention-National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.

Abstract

High levels of stress or stress hormones have been reported to exacerbate a variety of human disorders of the cardiovascular, gastrointestinal, immune, reproductive, and nervous systems. In rats, high glucocorticoid levels have been reported to cause neuronal death and injury as well as enhance susceptibility to neurotoxic agents and attenuate repair mechanisms; however, the impact of high dosages of CORT in mice has not been fully evaluated. We investigated the ability of supraphysiological levels of CORT to cause hippocampal neuronal death, and to modulate the neurotoxicity of kainic acid (KA) in male C57BL/6J mice. Timed-release CORT pellets (10, 35, 100 mg/21 d) were implanted subcutaneously in the back of mice, and the sustained release of glucocorticoid caused involution of the thymus and decreased the weight of the spleen. Kainic acid caused stage 1 seizures that were unaffected by CORT; however, steroid treatment decreased KA-associated mortality. Little neuronal damage was detected by the cupric-silver neurodegeneration stain. Neurotoxicity caused by an intraperitoneal injection of 25mg/kg KA was attenuated by seven days of CORT pre-treatment. The KA-induced increase in cupric-silver staining, reactive gliosis, microglial activation, and blood-brain barrier disruption was attenuated indicating neuroprotection. Our data indicate supraphysiological levels of CORT do not cause neuronal death or injury in hippocampus of C57BL/6J mice and provide neuroprotection against KA-induced neural damage.

PMID:
19616023
DOI:
10.1016/j.neuro.2009.07.005
[Indexed for MEDLINE]
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