Elsevier

Brain Research

Volume 338, Issue 2, 15 July 1985, Pages 289-295
Brain Research

Kainic acid-induced seizures: Dose-relationship of behavioural neurochemical and histopathological changes

https://doi.org/10.1016/0006-8993(85)90159-3Get rights and content

Abstract

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 decar☐ylase 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.

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    Similar dose and recording schedule was followed for AMPA and its antagonist GAMS. Equimolar dose of kainic acid microinjection as that of the other two excitatory amino acids in the behaving rats caused seizure-like activity, circling behaviour and ultimately cell body lesion (Sperk et al., 1985). So we used a lower dose for kainic acid (0.06 nM) (Silveira and Graeff, 1992) in the other groups (n=5).

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We would like to dedicate this paper to Prof. Dr. H. Klupp on the occasion of his 65th birthday.

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