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
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