REGIONAL CEREBRAL CIRCULATION AND METABOLISM

区域脑循环和代谢

• 批准号: 6290512
• 负责人: LOUIS SOKOLOFF
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290512
• 关键词: Animalia; antipyrine; brain metabolism; deoxyglucose; glucose metabolism; magnetic resonance imaging; method development; positron emission tomography; radiotracer

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 in response to functional activation of neural pathways in the nervous system. Most of the work in this project during the last year has been directed at identifying the biochemical mechanisms of regulation of CBF. 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 first 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 later stations in multisynaptic pathways nitric oxide (NO) produced by neuronal NO synthase appears to play a role.PublicationsSokoloff, L.: Energetics of functional activation in neural tissues. Neurochem. Res. 24: 321-329; 1999.Sokoloff, L., Kuang, T-Y, Horinaka, N., and Kennedy, C.: Are cerebral circulation and energy metabolism really tightly coupled? In: Krieglstein, J. (Ed.): Pharmacology of Cerebral Ischemia 1998. medpharm Scientific Publishers, Stuttgart, 1999, pp. 3-16.Madsen, P. L., Cruz, N. F., Sokoloff, L., and Dienel, G. A. Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: Excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J. Cereb. Blood Flow Metab. 19: 393-400; 1999.Sokoloff, L.: Mapping cerebral functional activity with radioactive deoxyglucose.In: Adelman, G. and Smith B. (Eds.): Encyclopedia of Neuroscience, 2nd Edition.Elsevier, Amsterdam, 1999, pp. 1092-1101.Sokoloff, L.: Mechanisms of regulation of cerebral blood flow. In: Ito, U., Fieschi, C., Orzi, F., Kuroiwa, T., and Klatzo, I.(Eds.):Maturation Phenomenon in Cerebral Ischemia III. Defensive Mechanisms versus Apoptosis; Neuronal Recovery and Protection in Infarction. Springer, Berlin, 1999, pp. 291-307.Elman. I., Sokoloff, L., Adler, C.M., Weisenfeld, N.,and Breier, A.: The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers. Brain Res. 815: 243-249; 1999.Nakao, Y., Kuang, T.- Y., Cohen, D. M., Pettigrew, K. D., and Sokoloff, L.: Cerebral blood flow responses to somatosensory stimulation are unaffected by scopolamine in the unanesthetized rat. J. Pharmacol. & Exper. Therap. 290: 929-934; 1999. - iodoantipyrine; local cerebral blood flow; 14C deoxyglucose; adenosine receptors; adenosine; K+ channels; cerebral blood vessels

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，以确定大脑血流(CBF)和能量代谢的基本生化和生理机制，以响应神经系统中神经通路的功能激活。在过去的一年里，该项目的大部分工作都是针对确定CBF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第一突触的区域。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。在多突触通路的后期，神经元一氧化氮合酶产生的一氧化氮(NO)似乎发挥了作用。出版物：神经组织功能激活的能量学。神经化学。Sokoloff，L.，Kuang，T-Y，Horinaka，N.和Kennedy，C.：大脑循环和能量代谢真的紧密耦合吗？收录于：Krieglstein，J.(编辑)：脑缺血药理学1998。Medpharm Science出版商，斯图加特，1999，第3-16页，Madsen，P.L.，Cruz，N.F.，Sokoloff，L.和Dienel，G.A.在感觉刺激期间大脑氧/葡萄糖比率很低，在恢复期间高于正常水平：刺激期间过量的葡萄糖消耗不是乳酸从脑组织外流或在脑组织中积累的原因。J·雷伯。血液流动Metab。19：393-400；1999.索科洛夫，L.：用放射性脱氧葡萄糖绘制大脑功能活动图.摘自：Adelman，G.and Smith B.(编辑)：神经科学百科全书，第二版.爱思唯尔，阿姆斯特丹，1999，第1092-1101页.收录于：Ito，U，Fieschi，C.，Orzi，F.，Kuroiwa，T.，and Klatzo，I.(编辑)：脑缺血中的成熟现象III。防御机制与细胞凋亡；脑梗塞中的神经元恢复与保护。施普林格，柏林，1999年，第291-307页。埃尔曼。I，Sokoloff，L.，Adler，C.M.，Weisenfeld，N.和Breier，A.：药物剂量的2-脱氧葡萄糖对健康志愿者脑血流的影响。脑部研究815：243-249；1999.Nakao，Y.，Kuang，Tong-Y.，Cohen，D.M.，Pettigrew，K.D.，and Sokoloff，L.：未麻醉大鼠的脑血流对躯体感觉刺激的反应不受东莨菪碱的影响。J.药理学&Exper.塞拉普。290：929-934；1999。-碘安替比林；局部脑血流量；14C脱氧葡萄糖；腺苷受体；腺苷；钾通道；脑血管