Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice
2006; Elsevier BV; Volume: 1070; Issue: 1 Linguagem: Inglês
10.1016/j.brainres.2005.11.065
ISSN1872-6240
AutoresStanley A. Benkovic, James P. O’Callaghan, Diane B. Miller,
Tópico(s)Mitochondrial Function and Pathology
ResumoWe 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.
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