ROLE OF ADENOSINE IN CEREBRAL BLOOD FLOW REGULATION

腺苷在脑血流调节中的作用

• 批准号: 3472165
• 负责人: David G Van Wylen
• 金额: $ 10.61万
• 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/3472165
• 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。 具体来说，本节中描述的实验的目标 提案旨在阐明腺苷在局部细胞中的作用 CBF 的代谢调节。 腺苷的基础 CBF 调节的假设是大脑的预测 间质液（ISF）作为耦合的介质 腺苷由脑细胞释放到作用部位 脑血管系统。 尽管重要性已得到公认 脑 ISF 有助于我们了解腺苷在 CBF 的监管，该领域的进展受到以下因素的限制： 进入大脑 ISF 的实际困难 隔室以确定其成分。 然而， 利用最近开发的脑透析技术， 可以测定脑ISF的成分。 拟议的 实验将检验腺苷调节的假说 CBF 使用改良的脑透析技术 监测局部 CBF 和脑 ISF 腺苷的变化 专注。 拟议研究的具体目标是：1）开发 腺苷假说可以通过药理学方案 通过脑透析技术进行测试； 2）确定 腺苷在CBF调节中的作用-药理学- 引起局部代谢活动和局部CBF的变化； 3）到 确定腺苷在缺氧期间 CBF 调节中的作用； 4）开发清醒大鼠模型的脑透析技术； 5) 确定腺苷在CBF调节中的作用 清醒大鼠脑缺血后，并且； 6) 确定 腺苷在生理过程中CBF调节中的作用 激活有意识的老鼠的特定大脑区域。 本研究的意义有两个：1） 脑透析技术在脑病研究中的应用 脑循环，将获得关于 CBF代谢调节的基本机制 已取得进展，特别是关于腺苷在 CBF 中的作用 监管； 2）从以下内容中获得的基本见解 拟议的研究可能会导致治疗方案 与癫痫、缺氧和脑损伤相关的病理 缺血是可以治疗的。