This is an omnibus project that covers a number of studies on developmenting these methods to determine the basic chemical and physiological mechanisms that mediate the functional activation of brain blood flow and metabolism that are now used so extensively to study cognitive and other functions. Much of the work in this project during the last year has been directed at elucidating the chemical mechanisms of regulation of cerebral blood flow. These results have shown that adenosine receptors and K+ channels in vascular smooth muscle are involved and that adenosine production by alterations in brain tissue metabolism initiates a cascade of events that act on the adenosine receptors and ends in the opening of the K+ channels, membrane hyperpolarization, and smooth muscle relaxation in the cerebral blood vessel walls. Publications Dienel, G.A., Cruz, N.F., Adachi, K., Sokoloff, L., and Holden, J.E. (1997) Determination of local brain glucose level with [14C]methylglucose: Effects of glucose supply and demand. Am. J. Physiol. (Endocrinol. Metab. 36), 273: E839-E849. Takahashi, S., and Sokoloff, L. (1997) Role of nitric oxide in the regulation of cerebral blood flow in conscious rats. In: Ishimura, Y. (Ed.): Oxygen Homeostasis and its Dynamics, Springer-Verlag, Tokyo, pp. 545-563. Horinaka, N., Kuang, T-Y, Pak, H., Wang, R., Jehle, J., Kennedy, C., and Sokoloff, L. (1997) Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. J. Cereb. Blood Flow Metab 17: 1309-1318. In Press: Sokoloff, L., (In press) Mapping cerebral functional activity with radioactive deoxyglucose. In: Adelman, G., and Smith B., (Eds.): Encyclopedia of Neuroscience, Second Edition, Amsterdam, Elsevier. Clark, D.D. and Sokoloff, L. (In press) Circulation and energy metabolism of the brain. In: Siegel, G., Agranoff, B., Albers, R.W., and Fisher, S. (Eds.): Balsic Neurochemistry: Molecular, Cellular, and Medical Aspects, Sixth Edition, Lippincott-Raven, Philadelphia. Turkheimer, F., Sokoloff, L., Bertoldo, A., Lucignani, G., Reivich, M., Jaggi, L.J., and Schmidt, K. (In press) Estimation of uncertainty in components determined with spectral analysis. J. Cereb. Blood Flow Metab (accepted March 11, 1998). Sokoloff, L. (In press) Mechanisms of regulation of cerebral blood flow. In: Ito, U., Kirino, T., Kuroiwa, T., and Klatzo, I. (Eds.): Maturation Phenomenon in Cerebral Ischemia III. Defensive Mechanisms versus Apoptosis; Neuronal Recovery and Protection in Infarction, Springer, Berlin. Sokoloff, L. (In press) Energetics of functional activation in neural tissues. Neurochem. Res. (Accepted July 27, 1998). Sokoloff, L., Kuang, T-Y, Horinaka, N., and Kennedy, C. (In press) Are cerebral circulation and energy metabolism really tightly coupled? In: Krieglstein, J. (Ed.): Pharmacology of Cerebral Ischemia 1998. medpharm Scientific Publishers, Stuttgard, 1998. Madsen, P.L., Cruz, N.F., Sokoloff, L., and Dienel, G.A. (In press) 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. (Accepted August 14, 1998).

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH000882-31
Application #
6111106
Study Section
Special Emphasis Panel (LCM)
Project Start
Project End
Budget Start
Budget End
Support Year
31
Fiscal Year
1998
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Poremba, Amy; Saunders, Richard C; Crane, Alison M et al. (2003) Functional mapping of the primate auditory system. Science 299:568-72
Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki et al. (2003) Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo. Proc Natl Acad Sci U S A 100:4879-84
Esaki, Takanori; Suzuki, Hideyo; Cook, Michelle et al. (2003) Functional activation of cerebral metabolism in mice with mutated thyroid hormone nuclear receptors. Endocrinology 144:4117-22
Esaki, Takanori; Itoh, Yoshiaki; Shimoji, Kazuaki et al. (2002) Effects of dopamine receptor blockade on cerebral blood flow response to somatosensory stimulation in the unanesthetized rat. J Pharmacol Exp Ther 303:497-502
Cohen, David M; Wei, Jingna; O'Brian Smith, E et al. (2002) A method for measuring cerebral glucose metabolism in vivo by 13C-NMR spectroscopy. Magn Reson Med 48:1063-7
Esaki, Takanori; Itoh, Yoshiaki; Shimoji, Kazuaki et al. (2002) Blockade of K(ATP) channels with glibenclamide does not alter functional activation of cerebral blood flow in the unanesthetized rat. Brain Res 948:56-63
Itoh, Y; Esaki, T; Cook, M et al. (2001) Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease. J Neurochem 79:1217-24
Turkheimer, F; Pettigrew, K; Sokoloff, L et al. (2000) Selection of an adaptive test statistic for use with multiple comparison analyses of neuroimaging data. Neuroimage 12:219-29
Sokoloff, L (2000) In vivo veritas: probing brain function through the use of quantitative in vivo biochemical techniques. Annu Rev Physiol 62:24-Jan
Gotoh, J; Itoh, Y; Kuang, T Y et al. (2000) Negligible glucose-6-phosphatase activity in cultured astroglia. J Neurochem 74:1400-8

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