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Keywords:

  • MRS;
  • PET;
  • fMRI;
  • BOLD;
  • oxygen;
  • glucose;
  • lactate;
  • glycogen;
  • neurotransmitter

Abstract

  1. Top of page
  2. Abstract
  3. REFERENCES

In the unstimulated brain energy is primarily supplied by the oxidation of glucose. However the oxygen-to-glucose index (OGI), which is the ratio of metabolic rates of oxygen to glucose, CMRO2/CMRglc, diverges from the theoretical value of 6 as activity is increased. In vivo measurements of brain lactate show its concentration to increase with stimulation. The decreasing OGI with stimulation had led to the suggestion that activation, unlike resting activity, is supported by anaerobic glycolysis. To date a unifying concept that accommodates glucose oxidation at rest with lactate generation and OGI decrease during stimulation of brain is lacking. Furthermore, energetics that change with increasing activity are not consistent with a neuroenergetic model that has been proposed from 1-13C-glucose MRS experiments. That model, based upon in vivo MRS measurements and cellular studies by Pellerin and Magistretti, showed that glutamate neurotransmitter cycling was coupled to glucose oxidation over a wide range of brain activities from rest down to deep anesthesia. Here we reconcile these paradoxical observations by suggesting that anaerobic glucose consumption (which can provide energy rapidly) increases with activation to meet the power requirements of millisecond neuronal firing. It is proposed, in accord with our neuroenergetic model, that the extra glucose mobilized rapidly for glial clearance of glutamate, is not needed for the oxidative processes that are responsible for neuronal firing and glutamate release, and consequently it is effluxed as lactate. A stoichiometric relation between OGI and lactate concentration is derived from the neuroenergetic model, showing that the enhanced glucose uptake during activation is consistent with neuronal activity being energetically supported by glucose oxidation. Copyright © 2001 John Wiley & Sons, Ltd.

REFERENCES

  1. Top of page
  2. Abstract
  3. REFERENCES
Abbreviations used:
ATP

adenosine triphosphate

BOLD

blood oxygen level dependent

CMRglc

cerebral metabolic rate of glucose consumption

CMRglc(ox)

cerebral metabolic rate of glucose oxidation

CMRO2

cerebral metabolic rate of oxygen consumption

fMRI

functional magnetic resonance imaging

Km

lactate concentration at half-maximum efflux

L

lactate concentration

MRS

magnetic resonance spectroscopy

Na-K-ATPase

sodium–potassium ATP synthase

OGI

oxygen glucose index

PCr

creatine phosphate

PET

positron emission tomography

31P NMR

phosphorous-31-nuclear magnetic resonance; Vcyc, rate of glutamate to glutamine cycling

Vout

rate of lactate efflux

Vmax

maximum rate of lactate efflux