Abstract
The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow and metabolism was originally performed using the Kety-Schmidt method and this method still represent the gold standard by which subsequent methods have been evaluated. However, in its classical setting, the method overestimates cerebral blood flow. Studies of metabolic changes during activation must take this into account, and subsequent methods for measurement of regional glucose metabolism must be corrected accordingly in order to allow reliable quantitative comparisons of metabolite changes in activation studies. For studies of regional metabolic changes during activation quantification poses further difficulties due to limitation in resolution and partial volume effects.
In contrast to the tight coupling between regional glucose metabolism and cerebral blood flow, there is an uncoupling between flow and oxygen consumption as the latter only increases to a limited extend. The excess glucose uptake is thus not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation, and especially temporal relationships must be taken into account.
What triggers the flow increase during functional brain activation is not entirely elucidated. The demand for excess glucose uptake may be important and a possible oxygen deficit in tissue distant from the capillaries is probably of minor importance. The mechanism by which cerebral blood flow increases during activation may incorporate changes in glycolytic substrates or local changes in astrocytes or neurons that triggers the production of vasoactive substances.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Blomqvist G, Stone-Elander S, Halldin C, Roland PE, Widen L, Lindqvist M, Swahn CG, Langstrom B, Wiesel FA (1990) Positron emission tomographic measurements of cerebral glucose utilization using [1-11C]D-glucose. J Cereb Blood Flow Metab 10:467–483
Brodersen P, Paulson OB, Bolwig TG, Rogon ZE, Rafaelsen OJ, Lassen NA (1973) Cerebral hyperemia in electrically induced epileptic seizures. Arch Neurol 28:334–338
Brooks RA, Hatazawa J, Di Chiro G, Larson SM, Fishbein DS (1987) Human cerebral gluocse metabolism determined by positron emission tomography: a revisit. J Cereb Blood Flow Metab 7:427–432
Bryan RM Jr, You J, Phillips SC, Andresen JJ, Lloyd EE, Rogers PA, Dryer SE, Marrelli SP (2006) Evidence for two-pore domain potassium channels in rat cerebral arteries. Am J Physiol Heart Circ Physiol Aug 291(2):H770–H780
Buxton RB, Frank LR (1997) A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. J Cereb Blood Flow Metab 17:64–72
Choi IY, Gruetter R (2003) In vivo 13C NMR assessment of brain glycogen concentration and turnover in the awake rat. Neurochem Int 43(4–5):317–322
Cholet N, Pellerin L, Welker E, Lacombe P, Seylaz J, Magistretti P, Bonvento G (2001) Local injection of antisense oligonucleotides targeted to the glial glutamate transporter GLAST decreases the metabolic response to somatosensory activation. J Cereb Blood Flow Metab 21:404–412
Cohen PJ, Alexander SC, Smith TC, Reivich M, Wollman H (1967) Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man. J Appl Physiol 23:183–189
Cruz NF, Dienel GA (2002) High glycogen levels in brains of rats with minimal environmental stimuli: Implications for metabolic contributions of working astrocytes. J Cereb Blood Flow Metab 22(12):1476–1489
Dalsgaard MK, Quistorff B, Danielsen ER, Selmer C, Vogelsang T, Secher NH (2004) A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain. J Physiol 554:571–578
Dienel GA, Cruz NF (2003) Neighborly interactions of metabolically-activated astrocytes in vivo. Neurochem Int 43:339–354
Dirnagl U, Niwa K, Lindauer U, Villringer A (1994) Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide. Am J Physiol 267:H296–H301
Dringen R, Gebhardt R, Hamprecht B (1993) Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res 623:208–214
Filosa JA, Bonev AD, Straub SV, Meredith AL, Wilkerson MK, Aldrich RW, Nelson MT (2006) Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci 9(11):1397–1403
Fox PT, Raichle ME, Mintun MA, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activation. Science 241:462–464
Graham MM, Muzi M, Spence AM, O’Sullivan F, Lewellen TK, Link JM, Krohn KA (2002) The FDG lumped constant in normal human brain. J Nucl Med 43:1157–1166
Gruetter R (2003) Glycogen: the forgotten cerebral energy store. J Neurosci Res 74(2):179–183, Oct 15
Hasselbalch SG, Madsen PL, Hageman LP, Olsen KS, Justesen N, Holm S, Paulson OB (1996) Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol 270:E746–E751
Hasselbalch SG, Madsen PL, Knudsen GM, Holm S, Paulson OB (1998) Calculation of the FDG lumped constant by simultaneous measurements of global glucose and FDG metabolism in humans. J Cereb Blood Flow Metab 18:154–160
Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27(2):219–249
Hofmann M, Pichler B, Schölkopf B, Beyer T (2009) Towards quantitative PET/MRI: A review of MR-based attenuation correction techniques. Eur J Nucl Med Mol Imaging 36(Suppl 1): S93–S104
Huang SC, Phelps ME, Hoffman EJ, Sideris K, Selin CJ, Kuhl DE (1980) Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 238:E69–E82
Jueptner M, Weiller C (1995) Review: does measurement of regional cerebral blood flow reflect synaptic activity? Implications for PET and fMRI. Neuroimage 2:148–156
Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305(5680):99–103, Jul 2
Kety SS (1957) The general metabolism of the brain in vivo. In: Richter D (ed) Metabolism of the nervous system. Pergamon, New York, pp 221–236
Kety SS, Schmidt CF (1948) The nitrous oxide method for quantitative determinations of cerebral blood flow in man: theory, procedure, and normal values. J Clin Invest 27:476–483
Knudsen GM (1994) Application of the double-indicator technique for measurement of blood-brain barrier permeability in humans. Cerebrovasc Brain Metab Rev 6:1–30
Knudsen GM, Pettigrew KD, Paulson OB, Hertz MM, Patlak CS (1990) Kinetic analysis of blood-brain barrier transport of d-glucose in man: quantitative evaluation in the presence of tracer backflux and capillary heterogeneity. Microvasc Res 39(1):28–49
Knudsen GM, Paulson OB, Hertz MM (1991) Kinetic analysis of the human blood-brain barrier transport of lactate and its influence by hypercapnia. J Cereb Blood Flow Metab 11:581–586
Knutsson L, Börjesson S, Larsson EM, Risberg J, Gustafson L, Passant U et al (2007) Absolute quantification of cerebral blood flow in normal volunteers: correlation between xe-133 SPECT and dynamic susceptibility contrast MRI. J Magn Reson Imaging 26(4):913–920
Kuschinsky W, Paulson OB (1992) Capillary circulation in the brain. Cerebrovasc Brain Metab Rev 4:261–286
Kuwabara H, Evans AC, Gjedde A (1990) Michaelis-Menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F]fluorodeoxyglucose. J Cereb Blood Flow Metab 10:180–189
Lassen NA (1959) Cerebral blood flow and oxygen consumption in man. Physiol Rev 39:183–238
Law I, Iida H, Holm S, Nour S, Rostrup E, Svarer C, Paulson OB (2000) Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: II. Normal values and gray matter blood flow response to visual activation. J Cereb Blood Flow Metab 20:1252–1263
Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJ, Gibbs JM, Wise RJ, Hatazawa J, Herold S (1990) Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain 113(Pt 1):27–47
Loaiza A, Porras OH, Barros LF (2003) Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy. J Neurosci 23:7337–7342
Madsen PL, Holm S, Herning M, Lassen NA (1993) Average blood flow and oxygen uptake in the human brain during resting wakefulness: a critical appraisal of the Kety-Schmidt technique. J Cereb Blood Flow Metab 13:646–655
Madsen PL, Hasselbalch SG, Hagemann LP, Olsen KS, Bulow J, Holm S, Wildschiodtz G, Paulson OB, Lassen NA (1995) Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique. J Cereb Blood Flow Metab 15:485–491
Madsen PL, Linde R, Hasselbalch SG, Paulson OB, Lassen NA (1998) Activation-induced resetting of cerebral oxygen and glucose uptake in the rat. J Cereb Blood Flow Metab 18:742–748
Madsen PL, Cruz NF, Sokoloff L, Dienel GA (1999) 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
Magistretti PJ, Pellerin L (1996) Cellular mechanisms of brain energy metabolism. Relevance to functional brain imaging and to neurodegenerative disorders. Ann N Y Acad Sci 777: 380–387
Magistretti PJ, Pellerin L (1999) Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 354:1155–1163
Medina JM, Tabernero A (2005) Lactate utilization by brain cells and its role in CNS development. J Neurosci Res 79(1–2):2–10
Mintun MA, Raichle ME, Martin WR, Herscovitch P (1984) Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med 25(2):177–187
Muller-Gartner HW, Links JM, Prince JL, Bryan RN, McVeigh E, Leal JP, Davatzikos C, Frost JJ (1992) Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab 12:571–583
Ostergaard L, Smith DF, Vestergaard-Poulsen P, Hansen SB, Gee AD, Gjedde A, Gyldensted C (1998) Absolute cerebral blood flow and blood volume measured by magnetic resonance imaging bolus tracking: comparison with positron emission tomography values. J Cereb Blood Flow Metab 18:425–432
Paulson OB, Newman EA (1987) Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science 237:896–898
Paulson OB, Hasselbalch SG, Rostrup E, Knudsen GM, Pelligrino D (2010) Cerebral blood flow response to functional activation. J Cereb Blood Flow Metab 30(1):2–14
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91:10625–10629
Pellerin L, Magistretti PJ (2004) Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 10:53–62
Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55(12):1251–1262
Perlmutter JS, Powers WJ, Herscovitch P, Fox PT, Raichle ME (1987) Regional asymmetries of cerebral blood flow, blood volume, and oxygen utilization and extraction in normal subjects. J Cereb Blood Flow Metab 7(1):64–67
Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6:371–388
Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C, MacGregor RR, Shiue CY, Atkins H, Anand A et al (1985) Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab 5:179–192
Rothman DL, Sibson NR, Hyder F, Shen J, Behar KL, Shulman RG (1999) In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics. Philos Trans R Soc Lond B Biol Sci 354: 1165–1177
Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994) Localization of neuronal and glial glutamate transporters. Neuron 13:713–725
Roy CS, Sherrington CS (1890) On the regulation of the blood supply of the brain. J Physiol (Lond) 11:85–108
Schousboe A, Westergaard N, Sonnewald U, Petersen SB, Huang R, Peng L, Hertz L (1993) Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev Neurosci 15: 359–366
Smith D, Pernet A, Hallett WA, Bingham E, Marsden PK, Amiel SA (2003) Lactate: a preferred fuel for human brain metabolism in vivo. J Cereb Blood Flow Metab 23:658–664
Straub SV, Nelson MT (2007) Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 17(6):183–190
Takano T, Tian GF, Peng W, Lou N, Libionka W, Han X, Nedergaard M (2006) Astrocyte-mediated control of cerebral blood flow. Nat Neurosci 9(2):260–267
Voutsinos-Porche B, Bonvento G, Tanaka K, Steiner P, Welker E, Chatton JY, Magistretti PJ, Pellerin L (2003) Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37:275–286
Wolff J, Chao TI (2004) Cytoarchitectonics of nonneuronal cells in the central nervous system. In: Hertz L (ed) Non-neuronal cells of the nervous system: function and dysfunction. Elsevier, Amsterdam, pp 1–52
Zonta M, Sebelin A, Gobbo S, Fellin T, Pozzan T, Carmignoto G (2003) Glutamate-mediated cytosolic calcium oscillations regulate a pulsatile prostaglandin release from cultured rat astrocytes. J Physiol 553:407–414
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Hasselbalch, S.G., Paulson, O.B. (2012). The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo . In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_14
Download citation
DOI: https://doi.org/10.1007/978-1-4614-1788-0_14
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-1787-3
Online ISBN: 978-1-4614-1788-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)