Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures

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 3min, 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 5min, 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±12.1s to 15.5±1.0s. 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.