Inhalation of 5%CO_(2)and activation of ASIC1a:a potential therapeutic approach for Dravet syndrome  

作　　者：Qian Lu Qi Zhang Yangyang Wang Jia Wang Haiqing Zhao Qiuhong Wang Liping Zou 

机构地区：[1]Department of Pediatrics,First Hospital of Qinhuangdao,Hebei,066000,China [2]Department of Pediatrics,the First Medical Center,Chinese PLA General Hospital,Beijing,100853,China [3]Nankai University School of Medicine,Tianjin,300071,China

出　　处：《Acta Epileptologica》2025年第1期114-123,共10页癫痫学报(英文)

基　　金：supported by grants from the Beijing E-Town Cooperation&Development Foundation(YCXJ-JZ-2022–007).

摘　　要：Background Preferential activation of Acid-sensing ion channel 1a(ASIC1a)by acidosis promotes seizure termination.Studies have found that CO_(2)can reduce neuronal excitability and inhibit seizure activity.Dravet syndrome(DS)is a severe and catastrophic form of epilepsy primarily caused by monoallelic loss-of-function mutations in the SCN1A gene.Patients with DS suffer from frequent seizures,which can be triggered by fever and are often resistant to anti-seizure medications.Thus,this study aimed to explore the effect of inhaling 5%CO_(2)and activating ASIC1a against hyperthermia-induced seizures in a mouse model of DS(Scn1a^(+/-)).Methods Mice aged postnatal day 18–28 were divided into four groups:wild type(WT)+air,Scn1a^(+/-)+air,WT+CO_(2),and Scn1a^(+/-)+CO_(2).Hyperthermia-induced seizures were performed 60 min after gas inhalation.Neuronal damage was assessed using Nissl staining,whereas ASIC1a expression was evaluated through Western blot and immunofluorescence staining.Results In the hyperthermia-induced seizure tests,no seizures occurred in WT mice.All mice in the Scn1a^(+/-)+air groups experienced seizures.In the Scn1a^(+/-)+CO_(2)group,all but one mouse had seizures.CO_(2)inhalation shortened the duration of seizures in Scn1a^(+/-)mice,improved electroencephalogram discharge patterns,and reduced neuronal damage in the hippocampus.The ASIC1a protein was mainly expressed in hippocampal neurons,with minor expression observed in astrocytes.The level of hippocampal ASIC1a increased in the Scn1a^(+/-)+CO_(2)mice.Conclusions After CO_(2)inhalation,the expression of the ASIC1a protein in the hippocampus increased,the duration of hyperthermia-induced seizures was reduced in Scn1a^(+/-)mice,and the damage to hippocampal neurons was alleviated.

关 键 词：Dravet syndrome CO_(2) ASIC1a SEIZURE SCN1A 

分 类 号：R74[医药卫生—神经病学与精神病学]