Is xenon neuroprotective in a mouse model of ALS

描述（由申请人提供）：肌萎缩性侧索硬化症（ALS）是一种致命的进行性运动神经元退行性疾病。目前的治疗方案是不充分的，只能最低限度地提高生活质量和生存时间。迫切需要新的治疗方法来延长ALS患者的寿命，提高他们的生活质量。氙（Xe）气体在临床上被用作麻醉剂，它被认为是安全的，几乎没有副作用，现有数据表明，它可能通过几种机制在治疗上有用，以对抗神经退行性过程。因此，我们提出了一项初步的试点研究，以评估氙气在家族性ALS C57Bl/6 SOD1G93A模型中延缓运动损伤发作、减少细胞凋亡和胶质细胞活化的功效。我们假设连续吸入Xe会延缓C57Bl/6 SOD1G93A小鼠运动损伤的发展，减少细胞凋亡和胶质细胞活化。如果我们验证我们的假设，这将为优化C57Bl/6 SOD1G93A模型中Xe暴露条件的系统研究奠定基础，最终可能导致临床使用Xe治疗ALS。

DESCRIPTION (provided by applicant): Amyotrophic Lateral Sclerosis (ALS) is a fatal progressive motor neuron degeneration disease. Current treatment options are inadequate and only minimally improve quality of life and survival times. There is an acute need for novel treatments that prolong lifespans of ALS patients and improve their quality of life. Xenon (Xe) gas has been used clinically as an anesthetic, it is considered safe and induces few side effects, and data exist suggesting that it may be therapeutically useful via several mechanisms for counteracting neurodegenerative processes. Accordingly, we propose an initial pilot study to assess xenon efficacy for delaying onset of motor impairments and reducing apoptosis and glial activation in the C57Bl/6 SOD1G93A model of familial ALS. We hypothesize that continuous Xe inhalational exposure will delay development of motor impairments and reduce apoptosis and glial activation in C57Bl/6 SOD1G93A mice. Should we validate our hypotheses, this will set the stage for systematic investigations to optimize Xe exposure conditions in the C57Bl/6 SOD1G93A model, which could ultimately lead to the clinical use of Xe to treat ALS. PUBLIC HEALTH RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disorder with major public health implications. Xenon gas has been used clinically as an anesthetic and it may be useful for slowing ALS- associated neurodegeneration. This project aims to initially test whether xenon can slow or prevent the development of motor system dysfunction and markers of apoptosis and glial activation in the C57Bl/6 SOD1G93A mouse model of familial ALS.