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Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

Item Type:Article
Title:Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis
Creators Name:Schuchmann, S., Schmitz, D., Rivera, C., Vanhatalo, S., Salmen, B., Mackie, K., Sipilae, S.T., Voipio, J. and Kaila, K.
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 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.
Keywords:Animal Disease Models, Bicarbonates, Body Temperature, Brain, Carbon Dioxide, Febrile Seizures, Fever, Pregnancy, Respiratory Alkalosis, Animals, Rats
Source:Nature Medicine
Publisher:Nature Publishing Group
Page Range:817-823
Date:July 2006
Official Publication:https://doi.org/10.1038/nm1422
PubMed:View item in PubMed

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