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Decreased neuronal damage and glial reactivity in an animal model of stress.

Benkovic-SA; O'Callaghan-JP; Miller-DB
Toxicologist 2010 Mar; 114(1):126
Neuronal damage elicits responses from glia that can be modulated by high levels of stress hormones. We evaluated neuronal damage and the glial response following treatment of C57BL/6J mice with corticosterone (CORT) and kainic acid (KA). Male mice were implanted with 100 mg/21 d release CORT pellets. After 7 d, mice received an intraperitoneal injection of saline or 25 mg/kg KA, were scored for seizures for 4 h, and were allowed to recover for 24 h. Brains were sectioned at 60 microns to allow 3-D evaluation of cellular morphology, and were analyzed for neurodegeneration by the cupric-silver stain, for microglia by Iba-1 and CD68 immunohistochemistry, and for astrocytes by GFAP immunohistochemistry. KA treatment caused neuronal damage that was especially evident in hippocampus, cortex, and thalamus. CORT pretreatment decreased argyrophilic staining. Iba-1 immunohistochemistry revealed microglial cells that were homogeneously dispersed throughout all brain regions including saline-injected controls. In 3-D space, ramified microglial cells occupied a specific volume that contained processes from that cell only. KA treatment caused activation of microglia and initiated a phenotypic transformation into amoeboid phagocytes that contained large vacuoles of ingested debris. In 3-D space, activated microglia were surrounded by a buffer space presumably formed as cellular processes retracted. Iba-1 staining was decreased in animals treated with CORT alone or with CORT + KA. CD68 immunostaining was not observed in control mice; however, KA treatment caused punctate immunoreactivity that was dispersed throughout the cell body and processes. In CORT-treated animals, CD68 immunostaining was virtually absent, and in co-treated mice, immunoreactivity was decreased. Basal GFAP immunoreactivity was observed in control mice where astrocytes displayed long, thin processes. KA treatment resulted in increased GFAP immunostaining that was prevented by CORT pretreatment. These data indicate high dosages of corticosteroids decrease neuronal damage caused by KA and subsequent astro- and microglial activation.
Biological-effects; Biological-monitoring; Cell-biology; Cell-morphology; Cellular-reactions; Exposure-assessment; Exposure-levels; Exposure-methods; Laboratory-animals; Laboratory-testing; Microscopic-analysis; Nerve-tissue; Nervous-system-function; Neurohormones; Neurological-reactions; Neurological-system; Physiological-effects; Statistical-analysis; Stress; Toxic-effects; Toxic-materials
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The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division