KAINIC ACID-INDUCED SEIZURES - DOSE-RELATIONSHIP OF BEHAVIORAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL CHANGES

KAINIC ACID-INDUCED SEIZURES - DOSE-RELATIONSHIP OF BEHAVIORAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL CHANGES
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DOI:
10.1016/0006-8993(85)90159-3
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发表时间:
1985-01-01
期刊:
影响因子:
2.9
通讯作者:
HORNYKIEWICZ, O
HORNYKIEWICZ, O
中科院分区:
医学3区
文献类型:
--
作者:
SPERK, G;LASSMANN, H;HORNYKIEWICZ, O

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在不同剂量的神经毒素(皮下注射 3、6 和 10 mg/kg)下,研究了向大鼠全身注射红藻氨酸所引起的行为、神经化学和组织病理学变化。红藻氨酸的剂量与注射后 3 小时的急性神经化学变化程度(所研究的所有脑区域中 3,4-二羟基苯乙酸和 5-羟基吲哚乙酸水平增加以及去甲肾上腺素 [去甲肾上腺素] 水平下降)、急性组织病理学变化(整个前脑神经细胞收缩和凝结以及脑水肿)和行为改变程度(不动)程度呈正相关。湿狗颤抖和边缘癫痫)。然而,剂量反应曲线的斜率非常陡。晚期和不可逆的改变包括酶标记物谷氨酸脱羧酶和胆碱乙酰转移酶的损失,以及组织病理学上的不完全实质坏死和出血。然而,这些变化仅限于少数大脑区域,最重要的是海马体、杏仁核、内嗅皮层、梨状皮层和嗅球,而且仅在经历过严重惊厥的动物中可见。在这种颞叶癫痫动物模型中,不可逆的脑损伤可能不是仅仅由红藻氨酸的直接作用引起的,而是可能至少部分由额外的继发发病机制引起。
Behavioral, neurochemical and histopathological changes induced by systemic injection of kainic acid into rats, were investigated at various doses of the neurotoxin (3, 6 and 10 mg/kg s.c.). There was a positive correlation between the dose of kainic acid and the extent of both the acute neurochemical changes 3 h after the injection (increases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid levels and a decrease in noradrenaline [norepinephrine] levels in all brain regions investigated), the acute histopathological changes (shrinkage and condensation of nerve cells and brain edema in the entire forebrain) and the extent of behavioral alterations (immobility wet dog shakes and limbic seizures). However, the slope of the dose-response curves were very steep. Late and irreversible alterations included losses of the enzyme markers glutamic acid decarboxylase and choline acetyltransferase and, histopathologically, incomplete parenchymal necrosis and hemorrhages. These changes, however, were restricted to a few brain regions, the most important being the hippocampus, amygdala, entorhinal and pyriform cortex and olfactory bulb, and they were seen only in animals which had undergone severe convulsions. The irreversible brain lesions in this animal model of limric (temporal lobe) epilepsy may not be solely induced by a direct action of kainic acid, but may be caused, at least in part, by additional, secondary pathogenetic mechanisms.