Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice.
Benkovic-SA; O'Callaghan-JP; Miller-DB
Brain Res 2006 Jan; 1070(1):215-231
We evaluated regional neuropathological changes in adult and aged male mice treated systemically with kainic acid (KA) in a strain reported to be resistant to excitotoxic neuronal damage, C57BL/6. KA was administered in a single intraperitoneal injection. Adult animals were dosed with 35 mg/kg KA, while aged animals received a dose of 20 mg/kg in order to prevent excessive mortality. At time-points ranging from 12 h to 7 days post-treatment, animals were sacrificed and prepared for histological evaluation utilizing the cupric-silver neurodegeneration stain, immunohistochemistry for GFAP and IgG, and lectin staining. In animals of both ages, KA produced argyrophilia in neurons throughout cortex, hippocampus, thalamus, and amygdala. Semi-quantitative analysis of neuropathology revealed a similar magnitude of damage in animals of both ages, even though aged animals received less toxicant. Additional animals were evaluated for KA-induced reactive gliosis, assayed by an ELISA for GFAP, which revealed a 2-fold elevation in protein levels in adult mice, and a 2.5-fold elevation in aged animals. Histochemical evaluation of GFAP and lectin staining revealed activation of astrocytes and microglia in regions with corresponding argyrophilia. IgG immunostaining revealed a KA-induced breach of the blood-brain barrier in animals of both ages. Our data indicate widespread neurotoxicity following kainic acid treatment in C57BL/6J mice, and reveal increased sensitivity to this excitotoxicant in aged animals.
Laboratory-animals; Animal-studies; Animals; Neuropathology; Brain-damage; Neurotoxic-effects; Neurophysiology; Neurotoxins; Neurotoxicity; Age-factors
Toxicology and Molecular Biology Branch, Centers for Disease Control and Prevention-National Institute for Occupational, Safety and Health, Mailstop 3014, 1095 Willowdale Road, Morgantown, WV 26505, USA
Research Tools and Approaches: Exposure Assessment Methods