Sensitive Indicators of Injury Reveal Hippocampal Damage in C57BL/6J Mice Treated with Kainic Acid in the Absence of Tonic-Clonic Seizures

Details

• Personal Author:
  Benkovic SA ; Miller DB ; O'Callaghan JP
• Description:
  Sensitive indices of neural injury were used to evaluate the time course of kainic acid (KA)-induced hippocampal damage in adult C57BL/6J mice (4 months), a strain previously reported to be resistant to kainate-induced neurotoxicity. Mice were injected systemically with saline or kainate, scored for seizure severity (Racine scale), and allowed to survive 12 h, one, three, or seven days following which they were evaluated for neuropathological changes using histological or biochemical endpoints. Most kainate-treated mice exhibited limited seizure activity (stage 1); however, cupric-silver and Fluoro-Jade B stains revealed significant damage by 12 h post-treatment. Immunohistochemistry and immunoassay of glial fibrillary acidic protein and lectin staining revealed a strong treatment-induced reactive gliosis and microglial activation. Immunostaining for immunoglobulin G revealed a kainate-induced breach in the blood-brain barrier. Nissl and hematoxylin stains provided little information regarding neuronal damage, but revealed the identity of non-resident cells which infiltrated the pyramidal layer. Our data suggest sensitive indicators of neural injury evaluated over a time course, both proximal and distal to treatment, are necessary to reveal the full extent of neuropathological changes which may be underestimated by traditional histological stains. The battery of neuropathological indices reported here reveals the C57BL/6J mouse is sensitive to excitotoxic neural damage caused by kainic acid, in the absence of tonic-clonic seizures. [Description provided by NIOSH]
• Subjects:
  Animals Laboratories Nervous System Nervous System Diseases Nervous System Disorders Occupational Health Safety
• Keywords:
  Animal-studies Author Keywords: Excitotoxicity Central-nervous-system-disorders Gliosis Injuries Laboratory-animals Nervous-system-disorders Neuropathology Neurotoxic-effects Neurotoxicity Neurotoxicology Neurotoxins

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• ISSN:
  0006-8993
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  59-76
• Volume:
  1024
• Issue:
  1
• NIOSHTIC Number:
  nn:20025893
• Citation:
  Brain Res 2004 Oct; 1024(1-2):59-76
• Contact Point Address:
  Toxicology and Molecular Biology Branch, Centers for Disease Control and Prevention-National Institute for Occupational Safety and Health, 1095 Willowdale Road, Mailstop 3014, Morgantown, WV 26505, USA
• Email:
  dum6@cdc.gov
• CAS Registry Number:
  α-Kainic acid (CAS RN 487-79-6)
• Federal Fiscal Year:
  2005
• Peer Reviewed:
  True
• Source Full Name:
  Brain Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:925c76787df8f10a7d7b84d55b62cdb76956eb75b190572c4c7d311b5b09446a836a87caeea3a41f2261fe91c2dc46def9a306ce41b50a21018e7446e102cfa5
• Download URL:
  https://stacks.cdc.gov/view/cdc/197080/cdc_197080_DS1.pdf
• File Type:
  [PDF - 1.83 MB ]