ONLY CERTAIN ANTICONVULSANTS PROTECT AGAINST KAINATE NEUROTOXICITY

  • 1 January 1981
    • journal article
    • research article
    • Vol. 3  (3) , 355-361
Abstract
Kainic acid (KA), a heterocyclic structural analog of the putative excitatory neurotransmitter, glutamate (Glu), powerfully mimics many neuroexcitatory and neurotoxic properties of Glu. KA differed from Glu and its straight chain excitotoxic analogs in inducing a limbic seizure-brain damage syndrome when administered s.c. (12 mg/kg) to adult rats. This syndrome consisted of sustained seizures, resembling amygdaloid kindled seizures and acute destruction of neural elements in limbic brain regions (amygdala, olfactory cortex, hippocampus, lateral septum and several thalamic nuclei). Early changes consisted of massive edematous swelling of glia and neuronal dendrites and swelling or dark cell changes in neuronal somata, with subsequent necrosis of many neurons. Pretreatment with morphine markedly enhanced the convulsant and brain damaging actions of KA. Pretreatment with 2 anticonvulsants (diazepam or phenobarbital) markedly reduced the seizure and brain damaging actions of KA; 2 other anticonvulsants (phenytoin or valproic acid) failed to suppress either phenomenon. A seizure mechanism caused much of the limbic brain damage induced by systemic KA and the toxic mechanism may have had 2 mutually reinforcing components, a glutamergic excitatory component and a GABAergic disinhibitory component.

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