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.

项目概要/摘要多发性硬化症 (MS) 是一种免疫介导的中枢神经系统神经退行性疾病，对髓磷脂造成局部损伤，导致功能丧失、残疾和生活质量下降。缓解疾病的药物可以帮助减少复发和新症状出现的频率，这种方法不足以从现有症状中获得最佳恢复，这是一种克服功能性的潜在方法。与现有运动缺陷相关的损伤是通过制定治疗策略来诱导该提案的目的是研究一种新型治疗干预的潜力—— 急性间歇性缺氧（AIH）——已显示出增强人神经可塑性的重大前景与脊髓损伤有关，但尚未在 MS 中进行研究。刺激血清素途径并增强血清素受体活性的浓度。导致可塑性相关蛋白的合成增加，从而增强突触传递和驱动我们努力相信重复的 AIH 方案能否改善患有自闭症的个体的自愿肢体功能。 MS。我们还发现 AIH 会引起中枢神经系统内神经活动的变化。系统，这有助于治疗的可塑性，我们使用双盲、假手术控制来测试这个假设。和交叉试验，对象是患有已确定的运动缺陷和受控复发活动的多发性硬化症患者给予轻度剂量的间歇性缺氧（或假缺氧）五天，我们检查所产生的影响。通过立即和干预后 1 周量化力量、功能和步行表现的变化。我们还使用先进的功能磁共振成像技术来测量神经的变化踝关节自愿屈曲期间的激活和休息时躯体运动皮层的内在连接性，在成功的运动康复策略中，两者都显示出可塑性相关的变化。将监测入组时和干预后 1 周的扫描，以发现新疾病活动的放射学迹象作为参与者安全监控的一部分，该提案将确定启动中央的程度。神经系统采用已知可诱导可塑性的方法改善了多发性硬化症的功能，并提供了证据从这项工作中获得的见解将为驱动这些治疗效果的神经机制提供信息。开发更有效的疗法，将日常 AIH 与特定任务训练相结合，以改善多发性硬化症患者的功能和生活质量。