难治性癫痫持续状态（RSE）为神经科一急危重症，在现有抗惊厥药物治疗下，死亡率常常超过35%，探索新的快速起效的治疗方法十分迫切。近期我课题组预实验发现氢气可快速终止小鼠RSE，且在酸敏感离子通道1a(ASIC1a)基因敲除小鼠中效果明显减弱，已知ASIC1a仅在病理状态组织酸化后被激活，介导非NMDA受体依赖性的Na+/Ca2+内流，与细胞兴奋性密切相关，提示：氢气可能通过调控脑内ASIC1a功能治疗RSE。藉此我们拟在前期工作基础上，采用经典RSE动物模型，首先探讨不同给氢方式对小鼠RSE的疗效以及神经保护性作用；进而观察RSE模型中氢气治疗前后小鼠海马ASIC1a的表达、磷酸化及膜转运变化，最后采用分子生物学及电生理技术探索氢气对不同细胞上ASIC1a通道功能的调控作用以及可能的机制。本项目的完成将为临床治疗RSE提供一快速有效的新方法。

Refractory Status Epilepticus is one of the most life-threatening neurologic emergencies, with the mortality rate of more than 35 percent under the existing anticonvulsant treatments, thus it is urgent to explore a new fast and effective treatment. Recently we found that hydrogen gas could quickly terminate RSE in mice, but this effect was significantly attenuated in acid-sensing ion channel-1a (ASIC1a) knock-out mice. It is well known that ASIC1a was only activated in tissue acidification under pathology, mediating the NMDA receptor-independent Na+/Ca2+ internal flow, which is closely related to cellular excitability. So the above evidence suggests that hydrogen gas may terminate RSE through regulating ASIC1a. Based on the preliminary work, we will firstly investigate the efficiency of different hydrogen gas administrations on RSE models as well as their neuroprotective effects. Then we will observe the changes of expression profile, trafficking and function of ASIC1a in the hippocampus of RSE mice before and after hydrogen gas treatments. Finally, we will further explore the regulation effect of hydrogen on the ASIC1a function in different cells as well as its possible mechanisms by molecular biology and electrophysiological technique. Our study will provide a new, fast and effective treatment for RSE.