Cerebral Response to Sustained Hypoxia

大脑对持续缺氧的反应

基本信息

批准号：
7437279
负责人：
DAVID DUBOWITZ
金额：
$ 42.53万
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 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7437279
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 Condition 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 Range Rate Research Research Personnel Resistance Risk Role Standards of Weights and Measures Stimulus Swelling System Testing Thinking Time Tissues Water base brain volume cerebrovascular cohort day 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脑缺氧的生理后果，以及正常稳态机制的失败如何进展为疾病。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，因此为了研究缺氧本身的脑稳态机制，重要的是将它们与潜在共存的多系统疾病分开进行检查。在本提案中，我们使用高原引起的缺氧（急性高山病 - AMS）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。该提议从传统的高海拔研究和脑生理学的功能性 MRI 研究中得出了假设。我们将通过实验测试这些现有模型，以解释从缺氧暴露到脑部疾病的进展。我们的具体目标是测量健康个体对急性（<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，并定义时间依赖性生理反应对缺氧的反应。使用脑生理学的 MRI 测量（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成部分。为了系统地评估正常生理反应的时间进程，这些测量将在一系列急性和持续的缺氧暴露下进行。测量将在同一组人类受试者中进行（包括 AMS 易感者和 AMS 抵抗者）。这些研究将提供大脑对缺氧的生理反应的全面了解，以及为什么有些人能够更好地适应低氧水平——我们将为理解为什么疾病患者对缺氧的反应不同奠定基础。设计适当的临床干预措施来治疗慢性脑缺氧衰退取决于这种全面的理解。