Mechanisms of Regulation of Cerebral Blood Flow

脑血流调节机制

• 批准号: 6927146
• 负责人: RICHARD J TRAYSTMAN
• 金额: $ 142.66万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927146
• 关键词: brain circulation; brain injury; cerebral ischemia /hypoxia; laboratory mouse; neuropathology

DESCRIPTION (provided by the applicant): The overall goal of this proposal is to define mechanisms of neuronal injury following focal and global cerebral ischemia in adult and pediatric animals. The Program represents a multidisciplinary mechanistic approach involving interactive productive investigators with complimentary areas of expertise who have long been committed to studies of the cerebral circulation and ischemia. One major aim will be to integrate the activities of various disciplines such that the interrelationships will result in a greater scientific contribution than could be achieved than if each project were pursued individually. The major theme is that state-of-the-art molecular, genetic, cellular, neuropathologic, physiologic, and neurobehavioral approaches are proposed to examine the mechanisms of neuronal injury and neuroprotection from stroke and cardiac arrest/CPR (focal and global cerebral ischemia). We will determine the neuroprotective mechanisms associated with sigma receptor signaling, sex hormones, nitric oxide, antioxidants, and poly (ADP-ribose) polymerase (PARP). The Program has several important strengths: First, the investigators have a long history of interactive studies of the brain and its vasculature under normal and pathophysiologic conditions. Second,-preliminary data in each project indicate feasibility of our approaches and demonstrate evidence of integration of the old and new parts of the Program. Third, the investigators are leaders in the field concerning mechanisms of neuronal injury, cerebrovascular regulation, ischemia, and neuroprotection. Fourth, the investigators use sophisticated physiological approaches and molecular, genetic, cellular, neuropathological and neurobehavioral approaches which have been incorporated to facilitate novel insight into neuronal injury and neuroprotection. The Program consists of 4 projects: 1) Sigma receptor signaling in focal cerebral ischemia; 2) Gender differences in stroke; 3) PARP in cardiac arrest/CPR; and 4) Cardiac arrest/CPR - mechanisms of brain injury in the newborn. This program is supported by 3 Core facilities: 1) Administration; 2) Cells and Tissues-Culture and Neuropathology; and 3) Transgenic Animals.

描述（由申请人提供）：该提案的总体目标是确定成年和儿童动物局部和整体脑缺血后神经元损伤的机制。该计划代表了一种多学科机械方法，涉及具有互补专业领域的交互式富有成效的研究人员，他们长期致力于脑循环和缺血的研究。一个主要目标是整合不同学科的活动，从而使相互关系产生比单独开展每个项目所能实现的更大的科学贡献。 主要主题是提出最先进的分子、遗传、细胞、神经病理学、生理学和神经行为方法来研究中风和心脏骤停/CPR（局灶性和全脑缺血）的神经元损伤和神经保护机制。我们将确定与西格玛受体信号传导、性激素、一氧化氮、抗氧化剂和聚（ADP-核糖）聚合酶（PARP）相关的神经保护机制。 该计划有几个重要的优势：首先，研究人员在正常和病理生理条件下对大脑及其脉管系统进行交互研究有着悠久的历史。其次，每个项目的初步数据表明了我们的方法的可行性，并证明了该计划的新旧部分整合的证据。第三，研究人员是神经元损伤机制、脑血管调节、缺血和神经保护机制领域的领导者。第四，研究人员使用复杂的生理学方法以及分子、遗传、细胞、神经病理学和神经行为方法，这些方法被纳入以促进对神经元损伤和神经保护的新见解。 该计划由 4 个项目组成：1) 局灶性脑缺血中的 Sigma 受体信号转导； 2）脑卒中的性别差异； 3) PARP 在心脏骤停/CPR 中的应用； 4) 心脏骤停/心肺复苏 - 新生儿脑损伤的机制。该计划由 3 个核心设施支持：1) 行政管理； 2）细胞和组织-培养和神经病理学； 3) 转基因动物。