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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目概要血管功能障碍导致许多神经系统疾病的病理学，但目前解决这些因素的治疗方案还不够，该项目的总体目标是测试。一种新的干预措施有可能改善大脑的血液供应，从而减轻血管的影响急性间歇性缺氧（AIH）正在成为一种强大的疾病。改善整体心血管健康并促进神经可塑性的疗法，但它对人类的影响已知缺氧通常会影响血管生成和血流，并且尚不清楚。暴露于短暂的缺氧刺激可以“预先调节”其他器官的脉管系统，使其更有弹性这项研究检验了为期 3 周的每日 AIH 干预将带来有益的假设。人类大脑的血管可塑性将被招募来完成随机假手术。对照交叉试验评估每日 AIH 与假干预的影响。创新的高磁共振成像 (MRI) 方案，用于评估 AIH 对局部区域的有益影响人类脑血管生理学，使用先进的灌注成像和前瞻性靶向气体引起血管舒张反应的挑战 AIH 对大脑生理学的影响将通过以下方式确定。两个特定目标的干预前和干预后 MRI 扫描的比较 1) 相差 MRI 和多干预后 MRI 扫描。将进行标记延迟伪连续动脉旋转标记 MRI 来量化全脑和休息时的局部组织灌注和血管传输时间 2) 吸入缺氧和高碳酸血症气体挑战。将在 MRI 扫描期间进行，以测量脑血管反应性 (CVR)、与之前使用粗略指标（例如经颅多普勒）的研究不同。超声检查），动脉自旋标记 MRI 提供的区域洞察力对于跟踪成像方案还提供了 AIH 在未来患者研究中的有效性和安全性。最后，拟议的研究具有重要意义。因为我们的结果可能表明 AIH 是改善人类健康的强大而实用的工具这对于采用其他方法改变血管的患者尤其重要。由于认知或运动障碍，风险因素（例如有氧运动）可能难以应用。概念验证研究取得成功，AIH 将成为一种令人兴奋的促进脑血管的新干预措施可塑性并为许多神经系统疾病开辟新的治疗机会血管功能障碍涉及其中，包括多发性硬化症、帕金森病和多种形式的通过有益地改变这些患者的脑血管生理机能，AIH 有可能治疗痴呆。解决导致神经损伤进展的血管和神经血管病理学。