Behavioural, histopathological and neurochemical changes induced by systemic injection of
kainic acid (10 mg/kg, s.c.) were investigated in rats. The most pronounced behavioural changes were strong immobility ("
catatonia"), increased incidence of "wet dog shakes", and long-lasting generalized
tonic-clonic convulsions. The behavioural symptoms were fast in their onset and lasted for several hours. Two distinct phases of histopathological and neurochemical changes were observed. (1) Early partially reversible changes were seen up to 3 h after
kainic acid injection. They consisted of shrinkage and pyknosis of neuronal perikarya together with swelling of dendrites and axon terminals. These changes were accompanied by generalized signs of
edema throughout the whole brain. Neurochemically, there was a marked decrease in
noradrenaline levels (up to 70%) and an increase in levels of 5-hydroxyindoleacetic
acid,
3,4-dihydroxyphenylacetic acid and
homovanillic acid (up to 200%) in all analysed brain regions, suggesting a strongly increased firing rate of aminergic neurones during the period of
generalized seizures. These histological and neurochemical changes were found in all the brain regions examined; they were greatly reduced or only sporadically seen after 1-3 days, when the animals had recovered from the
seizures. (2) Late irreversible changes developed 24 h and later following
kainic acid injection. They consisted of incomplete tissue
necrosis with loss of nerve cells and oligodendrocytes,
demyelination, astroglial
scar formation, small perivenous
hemorrhages and extensive vascular sprouting. The changes were restricted to the pyriform cortex, amygdala, hippocampus (most pronounced in the CA1 sector), gyrus olfactorius lateralis, bulbus olfactorius and tuberculum olfactorium. Neurochemically, a selective decrease was seen in
choline acetyltransferase activity (40%) of the amygdala/pyriform cortex area, and of
glutamate decarboxylase activity in the dorsal hippocampus (45%) and amygdala/pyriform cortex (55%). No such changes were found in the frontal cortex and the striatum/pallidum. Since at these later time periods the widespread early changes in monoamine metabolism were mostly normalized, loss of
acetylcholine and
gamma-aminobutyric acid neurons in the affected brain regions represented a selective neurochemical change typical for this stage of
kainic acid action. The observed neurochemical and histopathological changes may be directly related to the excitotoxic and convulsive properties of
kainic acid. However,
brain edema resulting in herniation damage of the basal portions of the brain in addition to disturbances of microcirculation and +