ROLE OF ADENOSINE IN CEREBRAL BLOOD FLOW REGULATION

拟议研究的广泛、长期目标是 进一步加深我们对脑血流(CBF)调节的理解。 具体地说，本文件中描述的实验的目标是 建议阐明腺苷在局部的作用。 脑血流量的代谢调节。腺苷的基础 脑血流量调节的假说是预测大脑 间质液体(ISF)作为连接细胞的介质 脑细胞释放的腺苷到作用部位 脑血管系统。尽管人们认识到 脑内间质纤维化有助于我们理解腺苷在脑缺血中的作用 对于CBF的监管，这一领域的进展受到了 获取大脑ISF的实际困难 以确定其组成。然而， 随着最近开发的脑透析技术的使用， 可以测定大脑ISF的成分。建议数 实验将验证腺苷假说对 CBF使用脑透析技术的改进来 监测局部脑血流量和脑ISF腺苷的变化 集中精神。 拟议研究的具体目标是：1)开发 腺苷假说可以 用脑透析技术进行测试；2)确定 腺苷在脑血流调节中的作用-在药理学过程中- 引起局部代谢活性和局部CBF的变化；3) 确定腺苷在低氧时脑血流调节中的作用； 4)建立清醒大鼠模型的脑透析技术； 5)确定腺苷在脑血流量调节中的作用 清醒大鼠脑缺血后；6)测定 腺苷在生理性脑血流调节中的作用 清醒大鼠特定脑区的激活。 拟议研究的意义有两个：1)通过 脑透析技术在脑出血研究中的应用 脑循环，将获得有关脑循环的新信息 脑血流量代谢调节的基本机制 实现，特别是关于腺苷在CBF中的作用 监管；以及；2)从 拟议的研究可能导致治疗方案，通过以下方式 与癫痫、缺氧和脑部疾病相关的病理学 缺血是可以治疗的。

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.