The biochemical mechanisms of the excitotoxicity of kainic acid. Free radical formation.
Kainic acid (KA) is a known potent neuroexcitotoxin, although the biochemical mechanism producing its underlying neurotoxic effect is not quite clear. Histopathological examination of gerbil brains 24 h after systemic injection of KA revealed severe neuronal lesions in different regions of the brain, especially the cerebellar and hippocampal areas. We have detected free radical formation in the brain 1 h after KA administration by using an in vivo spin trapping technique. We have also observed increased lipid peroxidation in the brain after KA-treatment by analyzing thiobarbituric acid reactive substances and conjugated diene formation. Diminished brain specific (Na+, K+)-ATPase activity was also found 2 h after KA injection and persisted to 24 h. It is possible that the free radical reaction is a primary cause of neuronal degeneration after KA administration.
Sun
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Department of Pharmacology, University of Missouri, Columbia 65212.
Cheng
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Bu
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Oldfield
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005609:Free Radicals; D005849:Gerbillinae; D006651:Histocytochemistry; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000201:enzymology; D017392:Thiobarbituric Acid Reactive Substances
D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D000254:Sodium-Potassium-Exchanging ATPase; D007608:Kainic Acid