Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia

1996 ◽  
Vol 270 (5) ◽  
pp. E746-E751 ◽  
Author(s):  
S. G. Hasselbalch ◽  
P. L. Madsen ◽  
L. P. Hageman ◽  
K. S. Olsen ◽  
N. Justesen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Carbohydrate Metabolism ◽  
Ketone Bodies ◽  
Regional Analysis ◽  
Oxygen Metabolism ◽  
Blood Concentrations ◽  
Positron Emission ◽  
The Brain

During starvation, brain energy metabolism in humans changes toward oxidation of ketone bodies. To investigate if this shift is directly coupled to circulating blood concentrations of ketone bodies, we measured global cerebral blood flow (CBF) and global cerebral carbohydrate metabolism with the Kety-Schmidt technique before and during intravenous infusion with ketone bodies. During acute hyperketonemia (mean beta-hydroxybutyrate blood concentration 2.16 mM), cerebral uptake of ketones increased from 1.11 to 5.60 mumol.100 g-1.min-1, counterbalanced by an equivalent reduction of the cerebral glucose metabolism from 25.8 to 17.2 mumol.100 g-1.min-1, with the net result being an unchanged cerebral uptake of carbohydrates. In accordance with this, global cerebral oxygen metabolism was not significantly altered (144 vs. 135 mumol.100 g-1.min-1). The unchanged global cerebral metabolic activity was accompanied by a 39% increase in CBF from 51.0 to 70.9 ml.100 g-1.min-1. Regional analysis of the glucose metabolism by positron emission tomography-[18F]fluoro-2-deoxy-D-glucose indicated that mesencephalon does not oxidize ketone bodies to the same extent as the rest of the brain. It was concluded that the immediate oxidation of ketone bodies induced a decrease in cerebral glucose uptake in spite of an adequate glucose supply to the brain. Furthermore, acute hyperketonemia caused a resetting of the coupling between CBF and metabolism that could not be explained by alterations in arterial CO2 tension or pH.

scholarly journals A Model for the Coupling between Cerebral Blood Flow and Oxygen Metabolism during Neural Stimulation

1997 ◽  
Vol 17 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Richard B. Buxton ◽  
Lawrence R. Frank
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Oxygen Metabolism ◽  
Neural Stimulation ◽  
Brain Capillaries ◽  
Tight Coupling ◽  
Positron Emission ◽  
General Mathematical Model ◽  
The Brain

A general mathematical model for the delivery of O2 to the brain is presented, based on the assumptions that all of the brain capillaries are perfused at rest and that all of the oxygen extracted from the capillaries is metabolized. The model predicts that disproportionately large changes in blood flow are required in order to support small changes in the O2 metabolic rate. Interpreted in terms of this model, previous positron emission tomography (PET) studies of the human brain during neural stimulation demonstrating that cerebral blood flow (CBF) increases much more than the oxygen metabolic rate are consistent with tight coupling of flow and oxidative metabolism. The model provides a basis for the quantitative interpretation of functional magnetic resonance imaging (fMRI) studies in terms of changes in local CBF.

Neuroimaging in Drug Discovery and Development: Paradigms for Accelerating New Drug Availability

2001 ◽  
Vol 14 (5) ◽  
pp. 407-415
Author(s):  
John T. Metz ◽  
Malcolm D. Cooper ◽  
Terry F. Brown ◽  
Leann H. Kinnunen ◽  
Declan J. Cooper
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Phase Ii ◽  
New Drugs ◽  
Central Effects ◽  
Drug Discovery And Development ◽  
Psychological Tasks ◽  
The Brain ◽  
Phase Iv

The process of discovering and developing new drugs is complicated. Neuroimaging methods can facilitate this process. An analysis of the conceptual bases and practical limitations of different neuroimaging modalities reveals that each technique can best address different kinds of questions. Radioligand studies are well suited to preclinical and Phase II questions when a compound is known or suspected to affect well-understood mechanisms; they are also useful in Phase IV to characterize effective agents. Cerebral blood flow studies can be extremely useful in evaluating the effects of a drug on psychological tasks (mostly in Phase IV). Glucose metabolism studies can answer the simplest questions about whether a compound affects the brain, where, and how much. Such studies are most useful in confirming central effects (preclinical and early clinical phases), in determining effective dose ranges (Phase II), and in comparing different drugs (Phase IV).

scholarly journals PET studies of changes in cerebral blood flow and oxygen metabolism after unilateral microembolization of the brain in anesthetized dogs.

Stroke ◽  
1987 ◽  
Vol 18 (1) ◽  
pp. 128-137 ◽  
Author(s):  
J Weyne ◽  
G De Ley ◽  
G Demeester ◽  
C Vandecasteele ◽  
F L Vermeulen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Oxygen Metabolism ◽  
Anesthetized Dogs ◽  
The Brain

scholarly journals Cerebral Blood Flow Response to Functional Activation

2009 ◽  
Vol 30 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Olaf B Paulson ◽  
Steen G Hasselbalch ◽  
Egill Rostrup ◽  
Gitte Moos Knudsen ◽  
Dale Pelligrino
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Oxidative Metabolism ◽  
Glucose Consumption ◽  
Oxygen Metabolism ◽  
Neural Activation ◽  
Metabolic Demand ◽  
Tight Coupling ◽  
Pronounced Increase

Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation.

Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

1989 ◽  
Vol 256 (6) ◽  
pp. E805-E810 ◽  
Author(s):  
C. Redies ◽  
L. J. Hoffer ◽  
C. Beil ◽  
E. B. Marliss ◽  
A. C. Evans ◽  
...  
Keyword(s):  
Blood Flow ◽  
Blood Volume ◽  
Ketone Bodies ◽  
Oxygen Metabolism ◽  
Whole Body ◽  
Transfer Coefficients ◽  
Oxygen Utilization ◽  
Whole Brain ◽  
Brain Glucose ◽  
The Brain

In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged.

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