Schuchmann Sebastian, Schmitz Dietmar, Rivera Claudio, Vanhatalo Sampsa, Salmen Benedikt, Mackie Ken, Sipilä Sampsa T, Voipio Juha, Kaila Kai
Department of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 1 (POB 65), 00014 Helsinki, Finland.
Nat Med. 2006 Jul;12(7):817-23. doi: 10.1038/nm1422. Epub 2006 Jul 2.
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.
热性惊厥在幼儿期很常见，而长时间（复杂性）热性惊厥与颞叶癫痫易感性增加有关。在暴露于高温的幼鼠中，对热性惊厥的病理生理后果已进行了广泛研究。然而，引发这些惊厥的机制尚不清楚。已知脑pH值升高会增强神经元兴奋性。在此我们表明，高温会导致未成熟大脑出现呼吸性碱中毒，诱发惊厥的阈值为0.2 - 0.3个pH单位。用5%的环境二氧化碳抑制碱中毒可在20秒内消除惊厥。二氧化碳还可预防海马体中高温惊厥的两种长期影响：I(h)电流上调和CB1受体表达上调。腹腔注射碳酸氢盐可密切模拟高温的作用。我们的研究揭示了引发高温惊厥的一种机制，并为与发热相关的癫痫综合征的研究和治疗提出了新策略。
