KAINIC ACID SEIZURES AND THE REVERSIBILITY OF CALCIUM LOADING IN VULNERABLE NEURONS IN THE HIPPOCAMPUS

Abstract

The threshold pathological changes in the rat hippocampus following systemic administration of kainic acid [KA] (12-15 mg/kg) were studied in relation to the duration of EEG seizure activity and Ca accumulation in post-synaptic neurons, using the oxalate-pyroantimonate method. The reversibility of the pathological changes and Ca loading was studied from 40 min to 48 h after the termination of seizure activity. Little or no changes were visible 2-3 h after 12 mg KA per kg, but changes were obvious in most hippocampi directly after 2-3.5 h of seizure activity induced by 15 mg KA per kg. These consisted of generalized swelling of perineuronal and perivascular astrocytic processes, neuronal hyperchromasia and microvacuolation and swelling of CA1 basal dendrites. Ischemic cell change occurred in a small number of pyramidal neurons. Ca accumulated in mitochondria of basal dendrites and in the soma of pyramidal neurons in CA1 and CA3. Astrocytic and dendritic swelling and mitochondrial calcium accumulation were rapidly reversed during 40 min of seizure suppression with diazepam. Ca accumulation in astrocytic processes recovered more slowly (.gtoreq. 4 h). After a recovery period of 24-48 h, ischemic cell changes were seen only in very occasional pyramidal neurons. The pattern of pathological changes is very similar to that seen after L-allylglycine or bicuculline-induced seizures. If the dendritic and other changes are a direct consequence of agonist actions at excitatory amino acid receptors (pre- or post-synaptic) then similar actions must be occurring in seizures induced by agents acting primarily on GABAergic inhibition.