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Letter
Nature Medicine 12, 817 - 823 (2006)
Published online: 2 July 2006 | doi:10.1038/nm1422
Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis
Sebastian Schuchmann1,7, Dietmar Schmitz2,7, Claudio Rivera1,3, Sampsa Vanhatalo4, Benedikt Salmen2, Ken Mackie5, Sampsa T Sipilä1, Juha Voipio1 & Kai Kaila1,6
Abstract
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 Ih 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.
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