Intermittent Hypoxia Initiated Motor Plasticity in Individuals with Multiple Sclerosis

间歇性缺氧引发多发性硬化症患者的运动可塑性

基本信息

批准号：
10593412
负责人：
Molly G Bright
金额：
$ 21.82万
依托单位：
REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-04 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10593412
关键词：
Acute Adverse effects Affect Air Ankle Autoimmune Automobile Driving Bilateral Brain imaging Brain-Derived Neurotrophic Factor Central Nervous System Central Nervous System Diseases Chronic Clinical Clinical Research Clinical Trials Combined Modality Therapy Communities Cross-Over Studies Cross-Over Trials Data Demyelinating Diseases Development Disease Disease remission Dose Double-Blind Method Effectiveness Enrollment Exposure to Frequencies Functional Magnetic Resonance Imaging Goals Hand Hypoxia Imaging Techniques Immune Individual Intervention Light Limb structure Longevity Lower Extremity MRI Scans Maps Measures Mediating Monitor Motor Motor Neurons Movement Multiple Sclerosis Myelin Neural Pathways Neurodegenerative Disorders Neuronal Plasticity North America Oxygen Patients Performance Persons Pharmaceutical Preparations Phase Physical activity Physiological Placebo Control Proteins Protocols documentation Publishing Quality of life Radiology Specialty Randomized Recovery Recovery of Function Rehabilitation therapy Relapse Reporting Research Research Personnel Research Priority Research Project Grants Respiratory physiology Rest Rodent Safety Seminal Serotonergic System Spinal cord injury Spinal cord injury patients Symptoms Synapses Synaptic Transmission Techniques Testing Therapeutic Therapeutic Effect Torque Training United States United States National Institutes of Health Walking Work burden of illness cognitive function common symptom design dexterity disability effective therapy functional disability functional improvement functional plasticity high reward high risk improved insight loss of function magnetic resonance imaging biomarker motor control motor deficit motor function improvement motor function recovery motor rehabilitation motor symptom multiple sclerosis patient neural neural circuit neuroimaging neuromechanism novel novel therapeutic intervention participant safety post intervention programs rehabilitation strategy respiratory serotonin receptor therapeutic development walking speed

项目摘要

PROJECT SUMMARY/ABSTRACT Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system that causes localized damage to myelin, resulting in loss of function, disability, and reduced quality of life. Although disease-modifying drugs can help reduce the frequency of relapses and onset of new symptoms, this approach is insufficient for optimal recovery from existing symptoms. One potential approach to overcome functional impairments related to existing motor deficits is through development of therapeutic strategies that induce neuroplasticity. The objective of this proposal is to investigate the potential of a novel therapeutic intervention — Acute Intermittent Hypoxia (AIH) — that has shown significant promise to enhance neuroplasticity in persons with spinal cord injury but has not yet been studied in MS. AIH constitutes a brief, repeated reduction in oxygen concentration which stimulates the serotonergic pathway and enhances activity of serotonin receptors. This results in increased synthesis of plasticity-related proteins that potentiate synaptic transmission and drive plasticity. We hypothesize that a repeated AIH protocol will improve voluntary limb function in individuals with MS. We also hypothesize that AIH will induce sustained changes in neural activity within the central nervous system, which contribute to therapeutic plasticity. We test this hypothesis using a double-blind, sham-controlled and crossover trial in MS patients with established motor deficits and controlled relapse activity who are administered mild doses of intermittent hypoxia (or sham hypoxia) for five days. We examine the resulting effects by quantifying changes in strength, function and walking performance immediately and 1-week post-intervention. We also use advanced functional magnetic resonance imaging techniques to measure changes in neural activation during voluntary ankle flexion and intrinsic connectivity in the somatomotor cortices at rest, which have both shown plasticity-related changes during successful motor rehabilitation strategies. Additional clinical MRI scans at enrollment and 1-week post-intervention will be monitored for radiologic signs of new disease activity as part of participant safety monitoring. This proposal will determine the extent to which priming the central nervous system with an approach known to induce plasticity improves function in MS, and provide evidence of the neural mechanisms driving these therapeutic effects. The insights gained from this work will inform the development of more effective therapies combining daily AIH with task specific training for improvement of function and quality of life in individuals with MS.

项目摘要/摘要多发性硬化症（MS）是中枢神经系统的免疫介导的神经退行性疾病，会对髓鞘造成局部损害，从而导致功能，残疾和生活质量降低。虽然改善疾病的药物可以帮助减少继电器的频率和新症状的发作，这种方法不足以从现有症状中恢复最佳。克服功能的一种潜在方法与现有电动机定义相关的障碍是通过发展理论的发展神经可塑性。该建议的目的是研究新型治疗干预的潜力 - 急性间歇性缺氧（AIH），这表现出了巨大的希望，可以增强人的神经可塑性由于脊髓损伤，但尚未在MS中进行研究。 AIH构成了短暂的，反复减少氧气刺激血清素能途径并增强5-羟色胺受体的活性的浓度。这导致增加与塑性相关蛋白的合成，从而潜在的突触传播和驱动可塑性。我们假设重复的AIH协议将改善患有多发性硬化症。我们还假设AIH会引起中枢神经内神经活动的持续变化系统，有助于治疗可塑性。我们使用双盲，假对照检验该假设以及已建立电动机的MS患者的分频试验定义和受控中继活动给予轻度剂量的间歇性缺氧（或假缺氧）五天。我们检查了产生的效果通过立即量化强度，功能和步行性能的变化以及干预后1周。我们还使用先进的功能磁共振成像技术来测量神经元的变化在静止的体育体皮层中，在自愿脚踝屈曲和固有连通性期间的激活两者都显示在成功的运动康复策略期间与可塑性相关的变化。额外的临床MRI 入学术和干预后1周的扫描将受到新疾病活动的放射线迹象的监测作为安全监控的一部分。该提议将确定启动中心的程度已知可诱导可塑性的方法的神经系统可改善MS的功能，并提供证据驱动这些治疗作用的神经机制。从这项工作中获得的见解将告知开发更有效的疗法，将每日AIH与特定任务培训相结合以改进具有MS的个体的功能和生活质量。