Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice.
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.
Benkovic
Stanley Anthony
SA
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.
O'Callaghan
James Patrick
JP
Miller
Diane Bemis
DB
D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D018690:Excitatory Amino Acid Agonists / Q000506:poisoning*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006651:Histocytochemistry / Q000379:methods; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000506:poisoning*; D037102:Lectins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology; D012640:Seizures / Q000209:etiology / Q000503:physiopathology; D013194:Staining and Labeling
D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D037102:Lectins; D007608:Kainic Acid