REGIONAL CEREBRAL CIRCULATION AND METABOLISM

这是一个综合性项目，涵盖了各种方法的开发、验证、改进和应用，以确定静息和神经通路功能激活时调节脑血流(CBF)和能量代谢的基本生化和生理机制。在过去的一年里，该项目的大部分工作都是针对确定CBF和新陈代谢调节的生化机制。今年的结果表明，沿着一条路径，有多种机制在不同的中继站运行。血管平滑肌中的腺苷受体参与初级突触的区域。功能激活过程中能量代谢改变产生的腺苷启动了一系列作用于腺苷受体的事件，最终导致脑血管壁K+通道开放、膜超极化和平滑肌松弛。在多突触通路的较高水平，神经元型一氧化氮合酶产生的一氧化氮(NO)似乎发挥了作用。腺苷和一氧化氮都不能完全解释功能激活引起的脑血流量增加，一定有其他因素参与。正在进行的研究表明，星形胶质细胞代谢可能与脑血流的调节密切相关。出版物Gotoh，J.，Itoh，Y.，Kuang，T.Y.，Cook，M.，Law，M.J.和Sokoloff，L.：培养的星形胶质细胞中可忽略的葡萄糖-6-磷酸酶活性。J·神经化学。74：1400-1408；2000。活体验证：通过使用定量的活体生化技术来探测大脑功能。安。菲西奥尔牧师。62：1-24；2000.索科洛夫，L.：脑血流和新陈代谢领域发展的历史回顾。程序第六届庆应义乌大学生命科学与医学国际研讨会，脑缺血血流。见Itoh，Y.，Law，Mona J.，and Sokoloff L.：Na+/H+交换器莫能菌素对星形胶质细胞内pH的影响。大脑研究。在新闻发布会上。郭东，J.，邝天勇，中尾勇，科恩，D.M.，梅尔泽P.，伊藤勇，Pak，H.，Pettigrew，K.，and Sokoloff L.脑循环对神经元激活的反应机制的地区差异。上午好。J.Physiol-心脏循环生理。在媒体上。

This is an omnibus project that covers a variety of studies on development, validation, refinement, and applications of methods to determine the basic biochemical and physiological mechanisms underlying the regulation of cerebral blood flow (CBF) and energy metabolism at rest and in response to functional activation of neural pathways. Most of the work in this project during the last year has been directed at identifying the biochemical mechanisms of regulation of CBF and metabolism. Results this year have shown that there are multiple mechanisms operating at different relay stations along a pathway. Adenosine receptors in vascular smooth muscle are involved in the regions of the primary synapses. Adenosine produced by altered energy metabolism during functional activation initiates a cascade of events that act on the adenosine receptors and ends in opening of K+ channels, membrane hyperpolarization, and smooth muscle relaxation in the cerebral blood vessel walls. At higher level stations in multisynaptic pathways nitric oxide (NO) produced by neuronal NO synthase appears to play a role. Neither adenosine nor nitric oxide account fully for the increases in cerebral blood flow evoked by functional activation, and other factors must be involved. Studies in progress indicate that astroglial metabolism may be intimately involved in the regulation of cerebral blood flow Publications Gotoh, J., Itoh, Y., Kuang, T.-Y., Cook, M., Law, M. J., and Sokoloff, L.: Negligible glucose-6-phosphatase activity in cultured astroglia. J. Neurochem. 74: 1400-1408; 2000. Sokoloff, L.: In vivo veritas: Probing brain function through the use of quantitative in vivo biochemical techniques. Ann. Rev. Physiol. 62: 1-24; 2000.Sokoloff, L.: A historical review of developments in the field of cerebral blood flow and metabolism. Proc. of 6th Keio University International Symposium for Life Sciences and Medicine, Ischemic Blood Flow in the Brain. In press Itoh, Y., Law, Mona J., and Sokoloff L.: Effects of the Na+/H+ exchanger monensin on intracellular pH in astroglia. Brain Res. In press. Gotoh, J., Kuang, T-Y, Nakao Y., Cohen, D. M., Melzer P., Itoh Y., Pak, H., Pettigrew, K.,and Sokoloff L. Regional differences in mechanisms of cerebral circulatory response to neuronal activation. Am. J. Physiol.-Heart Circulatory Physiol. In press.