Is xenon neuroprotective in a mouse model of ALS

氙对 ALS 小鼠模型有神经保护作用吗

基本信息

批准号：
8360816
负责人：
Marc J Kaufman
金额：
$ 7.9万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
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/8360816
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

项目摘要

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.

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。目前的治疗方案不足，只能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 患者的寿命并提高他们的生活质量。氙 (Xe) 气体已在临床上用作麻醉剂，它被认为是安全的，几乎不会引起副作用，并且现有数据表明，它可能通过多种机制来对抗神经退行性过程，从而具有治疗作用。因此，我们提出了一项初步试点研究，以评估氙在家族性 ALS 的 C57Bl/6 SOD1G93A 模型中延迟运动障碍发生、减少细胞凋亡和神经胶质活化的功效。我们假设连续吸入氙气会延缓 C57Bl/6 SOD1G93A 小鼠运动障碍的发展并减少细胞凋亡和神经胶质细胞活化。如果我们验证我们的假设，这将为系统研究奠定基础，以优化 C57Bl/6 SOD1G93A 模型中的 Xe 暴露条件，最终可能导致临床使用 Xe 治疗 ALS。公共卫生相关性：肌萎缩侧索硬化症 (ALS) 是一种慢性进行性神经退行性疾病，具有重大公共卫生影响。氙气已在临床上用作麻醉剂，可能有助于减缓 ALS 相关的神经变性。该项目旨在初步测试氙是否可以减缓或预防家族性 ALS 的 C57Bl/6 SOD1G93A 小鼠模型中运动系统功能障碍的发展以及细胞凋亡和胶质细胞激活的标志物。