Regional Neuropathology Following Kainic Acid Intoxication in Adult and Aged C57BL/6J Mice

Details

• Personal Author:
  Benkovic SA ; Miller DB ; O'Callaghan JP ; Benkovic SA ; Miller DB ; O'Callaghan JP
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Age Factors Animals Laboratories Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Age-factors Animal-studies Brain-damage Laboratory-animals Neuropathology Neurophysiology Neurotoxic-effects Neurotoxicity Neurotoxins
• ISSN:
  0006-8993
• Document Type:
  Text
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  215-231
• Volume:
  1070
• Issue:
  1
• NIOSHTIC Number:
  nn:20029874
• Citation:
  Brain Res 2006 Jan; 1070(1):215-231
• Contact Point Address:
  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
• Email:
  dum6@cdc.gov
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods ; Research Tools and Approaches: Exposure Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  Brain Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:adb68897a257adeb6ce1fc86592f913288b21448e0bec8b9108476d74dce890dd5799b52f02fc574015572f3722e76fdcdc8fe3c5a26fb691d22709778180e7a
• Download URL:
  https://stacks.cdc.gov/view/cdc/190769/cdc_190769_DS1.pdf
• File Type:
  [PDF - 1.27 MB ]