Is xenon neuroprotective in a mouse model of ALS

氙对 ALS 小鼠模型有神经保护作用吗

• 批准号: 8470738
• 负责人: Marc J Kaufman
• 金额: $ 7.62万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8470738
• 关键词: Acids; Acute; Acute Brain Injuries; Adverse effects; Amyotrophic Lateral Sclerosis; Anesthetic Gases; Anesthetics; Animals; Apoptosis; Asphyxia; Astrocytes; Behavioral; Biological Markers; Birth; Brain; Chronic; Clinical; Clinical Research; Data; Development; Disease; Dose; Exhibits; Exposure to; FDA approved; Familial Amyotrophic Lateral Sclerosis; Functional disorder; Gait; Gases; Genetic; Glial Fibrillary Acidic Protein; Glutamates; Heart Arrest; Hindlimb; Human; Investigation; Lead; Limb structure; Link; Liposomes; Longevity; Magnetic Resonance Imaging; Modeling; Motor; Mus; N-Methylaspartate; Nerve Degeneration; Neurodegenerative Disorders; Neurotransmitters; Patients; Performance; Pilot Projects; Play; Process; Public Health; Quality of life; Research; Riluzole; Role; Route; Safety; Serine Protease; Spinal Cord; Staging; Structure; System; Testing; Therapeutic Effect; Time; Traumatic Brain Injury; Treatment Efficacy; Tremor; Xenon; acute stroke; behavior test; caspase-3; design; improved; motor impairment; motor neuron degeneration; mouse model; neuron loss; novel; prevent; programs; receptor

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.

描述（由申请人提供）：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，只有最低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患者的寿命并改善他们的生活质量。氙气（Xenon）气体已在临床上用作麻醉剂，它被认为是安全的，并且引起很少的副作用，并且存在的数据表明，它可能通过几种机制在治疗上有用，用于抵消神经退行性过程。因此，我们提出了一个初步的试点研究，以评估氙的疗效，在C57 B1/6 SOD 1G 93 A模型的家族性ALS的运动障碍的延迟发作和减少细胞凋亡和神经胶质细胞活化。我们假设连续Xe吸入暴露将延迟C57 Bl/6 SOD 1G 93 A小鼠运动障碍的发展并减少细胞凋亡和神经胶质活化。如果我们验证了我们的假设，这将为系统研究奠定基础，以优化C57 B1/6 SOD 1G 93 A模型中的α暴露条件，这可能最终导致α治疗ALS的临床应用。