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

Sebastian Schuchmann, Dietmar Schmitz, Claudio Rivera, Sampsa Vanhatalo, Benedikt Salmen, Ken Mackie, Sampsa T. Sipila, Juha Voipio, Kai Kaila

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
JournalNature Medicine
Volume12
Issue number7
Pages (from-to)817-823
Number of pages7
ISSN1078-8956
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 311 Basic medicine
  • 118 Biological sciences
  • 515 Psychology

Cite this

Schuchmann, Sebastian ; Schmitz, Dietmar ; Rivera, Claudio ; Vanhatalo, Sampsa ; Salmen, Benedikt ; Mackie, Ken ; Sipila, Sampsa T. ; Voipio, Juha ; Kaila, Kai. / Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis. In: Nature Medicine. 2006 ; Vol. 12, No. 7. pp. 817-823.
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title = "Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis",
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.",
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Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis. / Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipila, Sampsa T.; Voipio, Juha; Kaila, Kai.

In: Nature Medicine, Vol. 12, No. 7, 2006, p. 817-823.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

AU - Schuchmann, Sebastian

AU - Schmitz, Dietmar

AU - Rivera, Claudio

AU - Vanhatalo, Sampsa

AU - Salmen, Benedikt

AU - Mackie, Ken

AU - Sipila, Sampsa T.

AU - Voipio, Juha

AU - Kaila, Kai

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

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