Mechanisms of Regulation of Cerebral Blood Flow

描述（由申请人提供）：本提案的总体目标是确定成人和儿童动物局灶性和全局性脑缺血后神经元损伤的机制。该计划代表了一个多学科的机械方法，涉及具有互补专业领域的互动生产性研究人员，他们长期致力于脑循环和缺血的研究。一个主要目标将是把各学科的活动结合起来，使相互关系产生比单独进行每一个项目所能取得的更大的科学贡献。主要的主题是采用最先进的分子、遗传、细胞、神经病理学、生理学和神经行为学方法来研究中风和心脏骤停/心肺复苏术（局灶性和全局性脑缺血）的神经元损伤和神经保护机制。我们将确定与sigma受体信号、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血管系统进行互动研究的历史悠久。其次，每个项目的初步数据表明了我们方法的可行性，并展示了该计划新旧部分整合的证据。第三，研究者在神经元损伤机制、脑血管调节、缺血和神经保护等方面处于领先地位。第四，研究人员使用复杂的生理方法和分子、遗传、细胞、神经病理学和神经行为方法，这些方法已被纳入促进对神经元损伤和神经保护的新见解。本项目包括4个项目：1)局灶性脑缺血中的Sigma受体信号；2)卒中的性别差异；3)心脏骤停/心肺复苏术中的PARP；4)心脏骤停/心肺复苏术——新生儿脑损伤的机制。该计划由3个核心设施支持：1)管理；2)细胞和组织-培养和神经病理学；3)转基因动物。

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.