Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis
Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis
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DOI：
10.1038/nm1422
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发表时间：
2006-07-01
期刊：
影响因子：
82.9
通讯作者：
Kaila, Kai
中科院分区：
文献类型：
--
作者：
Schuchmann, Sebastian;Schmitz, Dietmar;Kaila, Kai
热性惊厥在儿童早期是常见的，长期（复杂）热性惊厥与颞叶癫痫的易感性增加有关。热性惊厥的病理生理学后果已在暴露于高温的幼鼠中进行了广泛的研究。然而，触发这些癫痫发作的机制尚不清楚。已知大脑pH值的升高会增强神经元的兴奋性。在这里，我们表明，高温会导致呼吸道阻塞在未成熟的大脑，与癫痫发作诱导的阈值为0.2-0.3 pH单位。用5%的环境CO2抑制癫痫发作在20 s内消除了癫痫发作。CO2还阻止了海马中高热癫痫发作的两个长期效应：I-h电流的上调和CB 1受体表达的上调。通过腹腔注射碳酸氢盐密切模仿高温的影响。我们的工作指出了一种触发高热癫痫发作的机制，并为发热相关癫痫综合征的研究和治疗提出了新的策略。
Febrile seizures are frequent during early childhood, and prolonged ( complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I-h current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.