Lu Qian, Zhang Qi, Wang Yangyang, Wang Jia, Zhao Haiqing, Wang Qiuhong, Zou Liping
Department of Pediatrics, First Hospital of Qinhuangdao, Hebei, 066000, China.
Department of Pediatrics, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.
Acta Epileptol. 2025 Mar 6;7(1):19. doi: 10.1186/s42494-025-00204-8.
Preferential activation of Acid-sensing ion channel 1a (ASIC1a) by acidosis promotes seizure termination. Studies have found that CO 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 and activating ASIC1a against hyperthermia-induced seizures in a mouse model of DS (Scn1a).
Mice aged postnatal day 18-28 were divided into four groups: wild type (WT) + air, Scn1a + air, WT + CO, and Scn1a + CO. 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.
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 group, all but one mouse had seizures. CO 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 mice.
After CO 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.
酸中毒对酸敏感离子通道1a（ASIC1a）的优先激活可促进癫痫发作终止。研究发现，一氧化碳（CO）可降低神经元兴奋性并抑制癫痫发作活动。德雷维特综合征（DS）是一种严重的灾难性癫痫形式，主要由SCN1A基因的单等位基因功能丧失突变引起。DS患者频繁发作癫痫，可由发热触发，且通常对抗癫痫药物耐药。因此，本研究旨在探讨吸入5% CO并激活ASIC1a对DS（Scn1a）小鼠模型中热诱导癫痫发作的影响。
将出生后18 - 28天的小鼠分为四组：野生型（WT）+空气组、Scn1a +空气组、WT + CO组和Scn1a + CO组。吸入气体60分钟后进行热诱导癫痫发作实验。使用尼氏染色评估神经元损伤，通过蛋白质免疫印迹和免疫荧光染色评估ASIC1a表达。
在热诱导癫痫发作试验中，WT小鼠未发生癫痫发作。Scn1a +空气组的所有小鼠均出现癫痫发作。在Scn1a + CO组中，除一只小鼠外其他小鼠均出现癫痫发作。吸入CO缩短了Scn1a小鼠的癫痫发作持续时间，改善了脑电图放电模式，并减少了海马体中的神经元损伤。ASIC1a蛋白主要表达于海马神经元，在星形胶质细胞中有少量表达。Scn1a + CO小鼠海马体中ASIC1a水平升高。
吸入CO后，Scn1a小鼠海马体中ASIC1a蛋白表达增加，热诱导癫痫发作的持续时间缩短，海马神经元损伤减轻。
