Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-chome 5-1, Kita-ku, Okayama 700-8558, Japan.
Epilepsy Res. 2013 Jul;105(1-2):220-4. doi: 10.1016/j.eplepsyres.2013.01.003. Epub 2013 Jan 30.
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.
本研究旨在评估二氧化碳（CO2）对 Scn1a 突变相关热性惊厥的抗惊厥作用。我们检查了与 Scn1a 错义突变相关的高热诱导性惊厥（HISs）诱导后血气水平的生理变化。我们确定了吸入 5%或 10% CO2 治疗 HISs 的疗效。通过热水浴在 Scn1a 突变体和野生型（WT）大鼠中诱发 HISs。为了确定 CO2 吸入的抗惊厥作用，在 HISs 诱导后立即将大鼠置于充满空气或混合气体（含 5% CO2 或 10% CO2）的室中 3 分钟。我们还分析了 CO2 吸入结束时的血气水平。热水浴导致 WT 和 Scn1a 突变大鼠的二氧化碳分压（pCO2）显著降低和呼吸性碱中毒。在 100%的 Scn1a 突变大鼠中，在 5 分钟内诱发了 HISs，但在 WT 大鼠中均未诱发。与 WT 大鼠相比，Scn1a 突变大鼠表现出更高的 HISs 易感性，与呼吸性碱中毒有关。吸入 10% CO2 将惊厥持续时间从 62.6±12.1 s 缩短至 15.5±1.0 s。吸入 10% CO2 后的血气分析显示 pCO2 水平升高和呼吸性酸中毒。吸入 10% CO2 对 HISs 具有强大且快速的抗惊厥作用。
