KAINIC ACID-INDUCED SEIZURES - DOSE-RELATIONSHIP OF BEHAVIORAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL CHANGES
KAINIC ACID-INDUCED SEIZURES - DOSE-RELATIONSHIP OF BEHAVIORAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL CHANGES
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DOI:
10.1016/0006-8993(85)90159-3
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发表时间:
1985-01-01
期刊:
影响因子:
2.9
通讯作者:
HORNYKIEWICZ, O
中科院分区:
文献类型:
--
作者:
SPERK, G;LASSMANN, H;HORNYKIEWICZ, O
Behavioral, neurochemical and histopathological changes induced by systemic injection of kainic acid into rats, were investigated at various doses of the neurotoxin (3, 6 and 10 mg/kg s.c.). There was a positive correlation between the dose of kainic acid and the extent of both the acute neurochemical changes 3 h after the injection (increases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid levels and a decrease in noradrenaline [norepinephrine] levels in all brain regions investigated), the acute histopathological changes (shrinkage and condensation of nerve cells and brain edema in the entire forebrain) and the extent of behavioral alterations (immobility wet dog shakes and limbic seizures). However, the slope of the dose-response curves were very steep. Late and irreversible alterations included losses of the enzyme markers glutamic acid decarboxylase and choline acetyltransferase and, histopathologically, incomplete parenchymal necrosis and hemorrhages. These changes, however, were restricted to a few brain regions, the most important being the hippocampus, amygdala, entorhinal and pyriform cortex and olfactory bulb, and they were seen only in animals which had undergone severe convulsions. The irreversible brain lesions in this animal model of limric (temporal lobe) epilepsy may not be solely induced by a direct action of kainic acid, but may be caused, at least in part, by additional, secondary pathogenetic mechanisms.