ROLE OF ADENOSINE IN CEREBRAL BLOOD FLOW REGULATION

腺苷在脑血流调节中的作用

• 批准号: 3472161
• 负责人: David G Van Wylen
• 金额: $ 8.92万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3472161
• 关键词: adenosine; biological information processing; biological models; body fluids; brain metabolism; cerebral ischemia /hypoxia; diagnosis design /evaluation; dialysis; laboratory rat; neuropharmacology; nucleoside inhibitor; vascular smooth muscle

The broad, long-term objective of the proposed research is to further our understanding of cerebral blood flow (CBF) regulation. Specifically, the goal of the experiments described in this proposal is to elucidate the role of adenosine in the local metabolic regulation of CBF. Fundamental to the adenosine hypothesis for regulation of CBF is the prediction that cerebral interstitial fluid (ISF) serves as the medium which couples the adenosine released by brain cells to the site of action on the cerebral vasculature. Despite the recognized importance of cerebral ISF to our understanding of the role of adenosine in the regulation of CBF, progress in this area has been limited by the practical difficulty of gaining access to the cerebral ISF compartment in order to determine its composition. However, with the use of the recently developed brain dialysis technique, cerebral ISF composition can be determined. The proposed experiments will test the adenosine hypothesis for regulation of CBF using a modification of the brain dialysis technique to monitor changes in local CBF and cerebral ISF adenosine concentration. The specific aims of the proposed research are: 1) to develop pharmacological regimens by which the adenosine hypothesis can be tested with the brain dialysis technique; 2) to determine the role of adenosine in CBF regulation-during pharmacologically- induced changes in local metabolic activity and local CBF; 3) to determine the role of adenosine in CBF regulation during hypoxia; 4) to develop the brain dialysis technique in a conscious rat model; 5) to determine the role of adenosine in CBF regulation during and after cerebral ischemia in the conscious rat, and; 6) to determine the role of adenosine in CBF regulation during physiological activation of specific brain regions in the conscious rat. The significance of the proposed research is twofold: 1) by the application of the brain dialysis technique to the study of the cerebral circulation, new information will be gained as to the basic mechanisms by which metabolic regulation of CBF is achieved, specifically as to the role of adenosine in CBF regulation, and; 2) the fundamental insights attained from the proposed research may lead to therapeutic regimens by which pathologies associated with seizures, hypoxia, and cerebral ischemia can be treated.

拟议的研究的广泛，长期目标是 进一步，我们对脑血流（CBF）调节的理解。 具体而言，在此描述的实验的目标 建议是阐明腺苷在局部 CBF的代谢调节。 腺苷的基础 CBF调节的假设是脑的预测 间质流体（ISF）用作融合的介质 脑细胞释放到作用部位的腺苷 脑脉管系统。 尽管公认的重要性 大脑ISF我们对腺苷在 CBF的调节，该领域的进展受到 获得进入大脑ISF的实际困难 为了确定其成分。 然而， 通过使用最近开发的脑透析技术， 可以确定脑ISF组成。 提议 实验将测试腺苷假说的调节 CBF使用脑透析技术的修改为 监视本地CBF和大脑ISF腺苷的变化 专注。 拟议研究的具体目的是：1）开发 腺苷假设可以通过的药理方案 用脑透析技术进行测试； 2）确定 腺苷在CBF调节药理中的作用 - 诱发局部代谢活性和局部CBF的变化； 3）到 确定腺苷在缺氧期间CBF调节中的作用； 4）在有意识的大鼠模型中开发大脑透析技术； 5）确定腺苷在CBF调节中的作用和 在有意识的大鼠的脑缺血之后； 6）确定 腺苷在生理过程中CBF调节中的作用 在有意识的大鼠中激活特定的大脑区域。 拟议研究的意义是双重的：1） 将脑透析技术应用于研究 大脑循环，将获得有关有关的新信息 CBF代谢调节的基本机制为 专门针对腺苷在CBF中的作用 监管，并且； 2）从 拟议的研究可能会导致治疗方案 与癫痫发作，缺氧和脑有关的病理学 可以治疗缺血。