Improving Human Cerebrovascular Function Using Acute Intermittent Hypoxia

利用急性间歇性缺氧改善人脑血管功能

• 批准号: 10372685
• 负责人: Molly G Bright
• 金额: $ 24万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372685
• 关键词: Acute; Address; Adult; Aerobic; Aerobic Exercise; Affect; Air; Alzheimer' s Disease; Animal Model; Ankle; Architecture; Automobile Driving; Blood Pressure; Blood Vessels; Blood flow; Brain; Brain Injuries; Breathing; Carbon Dioxide; Cell Death; Cerebrovascular Physiology; Cerebrovascular system; Cerebrum; Chronic; Clinic; Clinical; Clinical Trials; Complex; Coronary Arteriosclerosis; Cross-Over Trials; Data; Dementia; Disease; Dose; Effectiveness; Elderly; Electromyography; Endothelial Cells; Evaluation; Exposure to; Future; Gases; Guidelines; Health; Home environment; Human; Hypercapnia; Hypoxia; Image; Impaired cognition; Impairment; Individual; Inhalation; Institution; Intervention; Label; Lower Extremity; Lung; MRI Scans; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Microvascular Dysfunction; Multiple Sclerosis; Nerve Degeneration; Neurologic; Neuronal Plasticity; Neurophysiology - biologic function; Organ; Oxygen; Parkinson Disease; Participant; Pathology; Patients; Perfusion; Persons; Phase; Physiological; Physiology; Predisposition; Protocols documentation; Randomized; Regional Perfusion; Research; Rest; Safety; Scanning; Sensory Deprivation; Spinal Cord; Spinal cord injury; Stimulus; Stroke; Synapses; System; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Transcranial Doppler Ultrasonography; Translating; Traumatic injury; Vascular Diseases; Vascular System; Vascular blood supply; Work; angiogenesis; arterial spin labeling; blood pressure elevation; blood pressure reduction; brain health; cardiovascular health; cerebral microvasculature; cerebrovascular; clinical translation; cohort; diffusion weighted; effectiveness evaluation; environmental change; exercise capacity; exercise regimen; follow-up; functional disability; functional improvement; high risk; hypertensives; imaging modality; improved; improved functioning; innovation; insight; motor function improvement; motor impairment; nervous system disorder; neurological pathology; neurological rehabilitation; neurovascular; novel; novel therapeutics; perfusion imaging; post intervention; prospective; recruit; relating to nervous system; repaired; resilience; response; safety and feasibility; stroke survivor; tool; vascular contributions; vascular risk factor; walking speed

PROJECT SUMMARY Vascular dysfunction contributes to the pathology of numerous neurological conditions, however current treatment options to address these factors are insufficient. The overall objective of this project is to test the potential of a novel intervention to improve the brain’s blood supply, thereby mitigating the vascular contributions to neurodegeneration and functional impairment. Acute Intermittent Hypoxia (AIH) is emerging as a powerful therapy to improve overall cardiovascular health and facilitate neural plasticity, however its impact on human cerebrovascular function is unclear. Hypoxia is known to generally influence angiogenesis and blood flow, and exposures to brief hypoxic stimuli can “precondition” the vasculature of other organs to be more resilient to severe hypoxic threat. This study tests the hypothesis that a 3-week daily AIH intervention will drive beneficial vascular plasticity in the human brain. Healthy participants will be recruited to complete a randomized sham- controlled crossover trial to assess the impact of daily AIH versus a sham intervention. This study employs a highly innovative magnetic resonance imaging (MRI) protocol to assess the beneficial effects of AIH on regional human cerebrovascular physiology, using advanced perfusion imaging and prospectively-targeted gas challenges to evoke vasodilatory responses. The impact of AIH on brain physiology will be determined through comparison of pre- and post-intervention MRI scans in two specific aims. 1) Phase-contrast MRI and multi-post- label-delay pseudo-continuous Arterial Spin Labeling MRI will be performed to quantify both whole-brain and regional tissue perfusion and vascular transit times at rest. 2) Inhaled hypoxia and hypercapnia gas challenges will be administered during MRI scanning to measure cerebrovascular reactivity (CVR), the responsiveness of blood vessels to a dilatory stimulus. Unlike previous studies that use gross metrics (e.g., transcranial Doppler ultrasonography), the regional insight provided by Arterial Spin Labeling MRI will be important for tracking the effectiveness and safety of AIH in future patient studies. The imaging protocol also provides a quantitative framework to optimize the AIH “dose” for a given cohort or individual. Finally, the proposed research is significant because our results may demonstrate that AIH is a powerful and practical tool for improving the health of the brain’s vasculature. This is of particular importance in patients where other approaches for modifying vascular risk factors (e.g., aerobic exercise) may be challenging to apply due to cognitive or motor impairment. If this proof-of concept study is successful, AIH will become an exciting new intervention for facilitating cerebrovascular plasticity and opening up new therapeutic treatment opportunities in the numerous neurological disorders where vascular dysfunction is implicated, including Multiple Sclerosis, Parkinson’s Disease, and several forms of dementia. By beneficially modifying cerebrovascular physiology in these patients, AIH has the potential to address the vascular and neurovascular pathologies that contribute to the progression of neurologic impairment.

项目摘要 血管功能障碍有助于许多神经系统疾病的病理学，但是 解决这些因素的治疗选择不足。该项目的总体目的是测试 新颖的干预措施可以改善大脑的血液供应，从而减轻血管贡献 神经变性和功能障碍。急性间歇性缺氧（AIH）正在成为一种强大的 改善整体心血管健康和紧急神经可塑性的疗法，但是它对人类的影响 脑血管功能尚不清楚。已知缺氧通常会影响血管生成和血流，并且 短暂的低氧刺激的暴露可以“前提”其他器官的脉管系统，以使其更具弹性 严重的低氧威胁。这项研究检验了以下假设，即每天3周的AIH干预将推动有益 人脑中的血管塑性。健康的参与者将被招募以完成随机假手术 - 受控的跨界试验，以评估每日AIH与假干预的影响。本研究员工 高度创新的磁共振成像（MRI）方案，以评估AIH对区域的有益影响 人脑脑血管生理学，使用先进的灌注成像和前瞻性气体 引起血管舒张反应的挑战。 AIH对脑生理的影响将通过 干预前和干预后MRI扫描的比较两个具体目的。 1）相对对比MRI和多柱 将进行标签 - 延迟伪连续的动脉自旋标记MRI，以量化全脑和 静止时区域组织灌注和血管过渡时间。 2）吸入缺氧和高碳酸盐气体挑战 将在MRI扫描期间给药以测量脑血管反应性（CVR）， 血管进行扩张刺激。与以前使用总指标的研究不同（例如，thrancranial多普勒 超声检查），通过动脉自旋标记MRI提供的区域洞察力对于跟踪很重要 AIH在未来的患者研究中的有效性和安全性。成像协议还提供了定量 为给定的队列或个人优化AIH的“剂量”的框架。最后，拟议的研究很重要 因为我们的结果可能表明AIH是改善健康状况的强大而实用的工具 大脑的脉管系统。这在其他修饰血管的患者中尤其重要 由于认知或运动障碍，可能会挑战危险因素（例如有氧运动）。如果这个 概念验证研究是成功的，AIH将成为促进脑血管的令人兴奋的新干预措施 可塑性并在许多神经系统疾病中开放新的治疗机会 实施了血管功能障碍，包括多发性硬化症，帕金森氏病和几种形式 失智。通过有益地修饰这些患者的脑血管生理学，AIH有可能 解决导致神经系统障碍进展的血管和神经血管病理学。