title: Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures.
abstract: The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined the efficacy of inhalation of 5% or 10% CO2 to treat HISs. HISs were evoked in Scn1a mutant and wild-type (WT) rats by hot water baths. To determine the anticonvulsant effect of CO2 inhalation, rats were placed in a chamber filled with air or mixed gas containing 5% CO2 or 10% CO2 for 3 min, immediately after the induction of HISs. We also analyzed the blood gas levels at the end of inhalation of CO2. Hot water bathing induced a significant reduction in the partial pressure of CO2 (pCO2) and respiratory alkalosis in the WT and Scn1a mutant rats. HISs were evoked in 100% of the Scn1a mutant rats within 5 min, but in none of the WT rats. The Scn1a mutant rats demonstrated a higher HISs susceptibility associated with respiratory alkalosis than the WT rats. Inhalation of 10% CO2 shortened the seizure duration from 62.6±12.1 s to 15.5±1.0 s. Blood gas analysis after the inhalation of 10% CO2 demonstrated an elevated pCO2 level and respiratory acidosis. Inhalation of 10% CO2 demonstrated a potent and fast-acting anticonvulsant effect against HISs.
authors: Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-chome 5-1, Kita-ku, Okayama 700-8558, Japan. iori@md.okayama-u.ac.jp
authors: Iori
authors: I
authors: Ohmori
authors: Keiichiro
authors: K
authors: Hayashi
authors: Haijiao
authors: H
authors: Wang
authors: Mamoru
authors: M
authors: Ouchida
authors: Naohiro
authors: N
authors: Fujita
authors: Takushi
authors: T
authors: Inoue
authors: Hiroyuki
authors: H
authors: Michiue
authors: Teiichi
authors: T
authors: Nishiki
authors: Hideki
authors: H
authors: Matsui
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage*; D005334:Fever / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D001239:Inhalation / Q000502:physiology; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D012640:Seizures / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568250:Scn1a protein, rat; D002245:Carbon Dioxide