Fuller T A, Olney J W
Neurobehav Toxicol Teratol. 1981 Fall;3(3):355-61.
Kainic acid (KA), a heterocyclic structural analog of the putative excitatory neurotransmitter, glutamate (Glu), powerfully mimics many of the neuroexcitatory and neurotoxic properties of Glu. KA differs from Glu and its straight chain "excitotoxic" analogs, however, in inducing a limbic seizure-brain damage syndrome when administered subcutaneously (12 mg/kg) to adult rats. This syndrome consists 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 consist of massive edematous swelling of glia and neuronal dendrites and either swelling or dark cell changes in neuronal somata, with subsequent necrosis of many of the neurons involved. Elsewhere we demonstrated that pretreatment with morphine markedly enhances both the convulsant and brain damaging actions of KA. Here we report that pretreatment with 2 anticonvulsants (diazepam or phenobarbital) markedly reduces both athe seizure and brain damaging actions of KA, whereas, two other anticonvulsants (phenytoin or valproic acid) fail to suppress either phenomenon. Our findings suggest that a seizure mechanism underlies much of the limbic brain damage induced by systemic KA and that the toxic mechanism may have two mutually reinforcing components--a glutamergic excitatory component and a GABAergic disinhibitory component.
海藻酸（KA）是假定的兴奋性神经递质谷氨酸（Glu）的杂环结构类似物，它能有力地模拟Glu的许多神经兴奋和神经毒性特性。然而，当对成年大鼠皮下注射（12毫克/千克）时，KA与Glu及其直链“兴奋性毒性”类似物不同，会诱发一种边缘叶癫痫 - 脑损伤综合征。该综合征包括持续的癫痫发作，类似于杏仁核点燃性癫痫发作，以及边缘脑区（杏仁核、嗅觉皮层、海马体、外侧隔核和几个丘脑核）神经元的急性破坏。早期变化包括胶质细胞和神经元树突的大量水肿性肿胀，以及神经元胞体的肿胀或暗细胞变化，随后许多受累神经元发生坏死。我们在其他地方证明，吗啡预处理可显著增强KA的惊厥和脑损伤作用。在此我们报告，两种抗惊厥药（地西泮或苯巴比妥）预处理可显著降低KA的癫痫发作和脑损伤作用，而另外两种抗惊厥药（苯妥英或丙戊酸）则无法抑制这两种现象。我们的研究结果表明，癫痫发作机制是全身性KA诱导的大部分边缘脑损伤的基础，并且毒性机制可能有两个相互增强的成分——一个谷氨酸能兴奋成分和一个γ-氨基丁酸能去抑制成分。
