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[大鼠杏仁核内注射各种兴奋性氨基酸所致的致痫性和神经毒性]

[Epileptogenicity and neurotoxicity induced by intra-amygdaloid injection of various excitatory amino acids in rats].

作者信息

Nakai H, Tanaka T, Yonemasu Y, Daita G, Fukuda H, Hashizume A

机构信息

Department of Neurosurgery, Asahikawa Medical College, Hokkaido, Japan.

出版信息

No To Shinkei. 1993 Mar;45(3):223-31.

PMID:8323816
Abstract

The electroencephalographic and histopathological changes following intra-amygdaloid injection of excitatory amino acids were examined in rats. Limbic seizure status was induced after injection of kainic acid (KA), domoic acid (DA), quisqualic acid (QA), alpha-allo-kainic acid (ALLO-KA) and D-glutamic acid (D-GA). The excitatory effect was found to be in the following order: KA > DA >> QA > ALLO-KA >> D-GA. D-GA caused only a transient paroxysmal discharge on EEG. However, seizure was not induced by an injection of L-glutamic acid (L-GA), D-aspartic acid (D-AA) and L-aspartic acid (L-AA). The minimum epileptogenic doses of these amino acids were defined and intra-amygdaloid injection of these doses were performed. Seven days following the injections, histopathological study was performed. These injection resulted in various degree of degeneration and neuronal cell loss of the pyramidal cells in the ipsilateral hippocampus in the following order of severity: DA > or = KA > D-GA > ALLO-KA > QA. These results indicate absence of correlation between epileptogenicity and histopathological changes. Non epileptogenic amino acids induced no pathological changes of hippocampus or the injected site. These results suggest that the severity of hippocampal damage induced by intra-amygdaloid injection of amino acids depends not only on the magnitude of the induced limbic seizure status but also on the difference of neuropharmacological properties of those amino acids in terms of the interaction with their receptors. Further studies are necessary to elucidate the mechanism of actions of these excitatory amino acids in relation to their receptor subtypes.

摘要

在大鼠中检测了杏仁核内注射兴奋性氨基酸后的脑电图和组织病理学变化。注射 kainic 酸(KA)、软骨藻酸(DA)、喹啉酸(QA)、α-别 kainic 酸(ALLO-KA)和 D-谷氨酸(D-GA)后诱发了边缘性癫痫状态。发现兴奋作用顺序如下:KA > DA >> QA > ALLO-KA >> D-GA。D-GA 仅在脑电图上引起短暂的阵发性放电。然而,注射 L-谷氨酸(L-GA)、D-天冬氨酸(D-AA)和 L-天冬氨酸(L-AA)未诱发癫痫发作。确定了这些氨基酸的最小致痫剂量,并进行了杏仁核内注射这些剂量的操作。注射后 7 天,进行了组织病理学研究。这些注射导致同侧海马锥体细胞出现不同程度的变性和神经元细胞丢失,严重程度顺序如下:DA > 或 = KA > D-GA > ALLO-KA > QA。这些结果表明致痫性与组织病理学变化之间不存在相关性。非致痫性氨基酸未引起海马或注射部位的病理变化。这些结果表明,杏仁核内注射氨基酸诱导的海马损伤严重程度不仅取决于诱发的边缘性癫痫状态的程度,还取决于这些氨基酸在与受体相互作用方面神经药理学特性的差异。需要进一步研究以阐明这些兴奋性氨基酸与其受体亚型相关的作用机制。

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