Behavioural, neurochemical and histopathological changes induced by systemic injection of
kainic acid 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 levels in all brain regions investigated), the acute histopathological changes (shrinkage and condensation of nerve cells and brain oedema in the entire forebrain) and the extent of behavioural alterations (immobility, 'wet dog shakes' and limbic
seizures). However, the slope of the dose-response curves was very steep. Late and irreversible alterations included losses of the
enzyme markers
glutamic acid decarboxylase and
choline acetyltransferase and, histopathologically, incomplete parenchymal
necrosis and haemorrhages. 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. It is suggested that the irreversible brain lesions in this animal model of limbic (
temporal lobe) epilepsy are not solely induced by a direct action of
kainic acid, but may be caused--at least in part--by additional, secondary pathogenetic mechanisms.