ROLE OF ADENOSINE IN CEREBRAL BLOOD FLOW REGULATION

拟议研究的广泛和长期目标是 进一步了解脑血流量（CBF）调节。 具体地说，本文中描述的实验的目标是 建议是阐明腺苷在局部 CBF的代谢调节。 腺苷的基础 关于CBF调节的假设是， 间质液（ISF）作为介质， 脑细胞释放的腺苷， 脑血管系统。 尽管公认的重要性， 脑ISF的研究有助于我们理解腺苷在 CBF的监管，这方面的进展受到限制， 进入脑ISF的实际困难 以确定其组成。 然而，在这方面， 通过使用最近开发的脑透析技术， 可以确定大脑ISF的组成。 拟议 实验将测试腺苷调节的假设， CBF使用脑透析技术的修改， 监测局部CBF和脑ISF腺苷的变化 浓度. 本研究的具体目标是：（1）开发 腺苷假说的药理学方案可以 用脑透析技术进行测试; 2）确定 腺苷在脑血流量调节中的作用--脑缺血-- 引起局部代谢活动和局部CBF的变化; 3） 确定腺苷在缺氧时CBF调节中的作用; 4)建立清醒大鼠脑透析模型; 5)确定腺苷在脑血流调节中的作用， 清醒大鼠脑缺血后，以及; 6）确定 腺苷在生理性脑血流调节中作用 激活清醒大鼠的特定脑区。 建议的研究的意义是双重的：1）由 脑透析技术在脑血管病研究中的应用 脑循环，将获得新的信息， CBF代谢调节的基本机制是 特别是腺苷在CBF中的作用 监管; 2）从监管中获得的基本见解 拟议的研究可能会导致治疗方案， 与癫痫发作、缺氧和脑 可以治疗局部缺血。

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.