Is xenon neuroprotective in a mouse model of ALS

描述(申请人提供)：肌萎缩侧索硬化症(ALS)是一种致命的进行性运动神经元变性疾病。目前的治疗选择是不够的，只能最小限度地改善生活质量和生存时间。迫切需要新的治疗方法来延长ALS患者的生命并提高他们的生活质量。氙气(Xe)已被用作临床麻醉剂，它被认为是安全的，并且几乎没有副作用，而且有数据表明，它可能通过几种机制对抗神经退化过程而在治疗上有用。因此，我们提出了一项初步的初步研究，以评估氙气在延缓C57BL/6 SOD1G93A家族性ALS模型中运动障碍的发生、减少细胞凋亡和胶质细胞激活方面的有效性。我们推测，持续的Xe吸入暴露将延缓C57BL/6 SOD1G93A小鼠运动损伤的发展，并减少细胞凋亡和神经胶质细胞的激活。如果我们验证我们的假设，这将为在C57BL/6 SOD1G93A模型中优化Xe暴露条件的系统研究奠定基础，这最终可能导致Xe用于临床治疗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.