Cerebral Response to Sustained Hypoxia

大脑对持续缺氧的反应

基本信息

批准号：
8074491
负责人：
DAVID DUBOWITZ
金额：
$ 44.67万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-15 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8074491
关键词：
Accounting Acetazolamide Acute Address Altitude Altitude Sickness Anatomy Biological Models Blood Volume Brain Brain Edema Carbon Dioxide Carbonic Anhydrase Inhibitors Cardiac Cerebral Hypoxia Cerebrovascular Circulation Cerebrum Chronic Clinical Core-Binding Factor Data Development Disease Edema Environmental air flow Exposure to Failure Figs - dietary Functional Magnetic Resonance Imaging Generations Genetic Transcription Goals Homeostasis Hypoxia Individual Intervention Intracranial Pressure Lead Left Lung Magnetic Resonance Imaging Measurement Measures Mechanics Mitochondria Modeling Outcome Oxygen Pathway interactions Patients Phosphorylation Physiological Physiology Precipitating Factors Process Production Research Research Personnel Resistance Risk Role Stimulus Swelling System Testing Thinking Time Tissues Water base brain volume cerebrovascular cohort design feeding hemodynamics human subject mathematical model pressure programs relating to nervous system response

项目摘要

DESCRIPTION (provided by applicant): Our overall goal is to understand the physiological consequences of global cerebral hypoxia, and how failure of the normal homeostatic mechanisms progresses to disease. To address this, it is first necessary to define the normal physiological responses to cerebral hypoxia. Cerebral hypoxia is the outcome of many disease processes (pulmonary, cardiac, cerebrovascular), and thus to investigate cerebral homeostasis mechanisms to hypoxia per se, it is important to examine them in isolation from potentially coexistent multi-system disease. In this proposal we use altitude-induced hypoxia (Acute Mountain Sickness - AMS) as a model system of isolated sustained hypoxia to study the normal physiological response mechanisms. This proposal draws hypotheses from traditional high altitude research and from functional MRI studies of cerebral physiology. We will experimentally test these existing models to explain the progression from hypoxic exposure to cerebral disease. Our specific aims are to measure the normal cerebral physiological response to acute (<6 hrs), short-term (2 days) and sustained (7 days) hypoxia (PIO2 = 90 Torr) in healthy individuals, and define the time-dependent physiologic response to hypoxia. Using MRI measurements of cerebral physiology (i.e. changes in CBF, CMRO2, CSF volume & edema) we will experimentally test individual components of the models. To systematically assess the time-course of the normal physiological responses, these measurements will be made over a range of acute and sustained hypoxic exposure. Measurements will be made in the same cohort of human subjects (encompassing AMS-susceptible andAMS-resistant individuals). These studies will provide a comprehensive picture of the cerebral physiological responses to hypoxia, and why some individuals are better able to acclimatize to low oxygen levels-we will establish a basis for understanding why patients with disease respond differently to hypoxia. Designing appropriate clinical interventions to treat chronic cerebral hypoxic decline hinges on such a comprehensive understanding.

描述（由申请人提供）：我们的总体目标是了解全球脑缺氧的生理后果，以及正常稳态机制的失败如何发展为疾病。为了解决这个问题，首先有必要定义对脑缺氧的正常生理反应。脑缺氧是许多疾病过程（肺，心脏，脑血管）的结果，因此要研究缺氧本身的脑稳态机制，重要的是要与潜在共存的多系统疾病分离进行检查。在此提案中，我们使用高度引起的缺氧（急性山疾病-AM）作为孤立持续缺氧的模型系统来研究正常的生理反应机制。该建议从传统的高空研究和脑生理学功能MRI研究中提取了假设。我们将通过实验测试这些现有模型，以解释从低氧暴露于脑疾病的过程。我们的具体目的是测量健康个体中对急性（<6小时），短期（2天）和持续（7天）缺氧（PIO2 = 90 TORR）的正常脑生理反应，并定义时间依赖时间的生理学反应。使用脑生理学的MRI测量值（即CBF，CMRO2，CSF体积和水肿的变化），我们将通过实验测试模型的各个组件。为了系统地评估正常生理反应的时间顺序，这些测量将在一系列急性和持续的低氧暴露范围内进行。测量将在同一人群中进行（包含AMS敏感的和抗Andams的个体）。这些研究将为缺氧的脑生理反应提供全面的了解，以及为什么有些人能够更好地适应低氧水平，这将建立一个基础，以理解为什么疾病患者对缺氧的反应不同。设计适当的临床干预措施来治疗慢性脑缺氧下降，这是如此全面的理解。