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 alkalosisSebastian Schuchmann1, 7, Dietmar Schmitz2, 7, Claudio Rivera1, 3, Sampsa Vanhatalo4, Benedikt Salmen2, Ken Mackie5, Sampsa T Sipilä1, Juha Voipio1 & Kai Kaila1, 61
Department of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 1 (POB 65), 00014 Helsinki, Finland. 2
Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Schumannstrasse 20/21, D-10119, Berlin, Germany. 3
Institute of Biotechnology, University of Helsinki, Viikinkaari 6 (POB 56), 00014 Helsinki, Finland. 4
Department of Clinical Neurophysiology, Children's Hospital, Helsinki University Central Hospital, Lastenlinnantie 2 (POB 280), 00029 HUS, Finland. 5
Department of Anesthesiology, University of Washington, 1959 NE Pacific Street (POB 356540), Seattle, Washington 98195-6540, USA. 6
Neuroscience Center, University of Helsinki, Viikinkaari 4 (POB 56), 00014 Helsinki, Finland
7
These authors contributed equally to this work.
Correspondence should be addressed to Kai Kaila kai.kaila@helsinki.fi 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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