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Front Neurosci. 2018 Sep 11;12:631. doi: 10.3389/fnins.2018.00631. eCollection 2018.

Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood.

Author information

1
Department of Anesthesiology, Yale School of Medicine, Yale University, New Haven, CT, United States.
2
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
3
Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, United States.
4
Department of Anesthesiology, Stony Brook University, Stony Brook, NY, United States.
5
Department of Translational Neurobiology, University of Southern Denmark, Odense, Denmark.
6
Department of Biomedical Engineering & Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, CT, United States.

Abstract

Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMRglucose-CMRO2 mismatch, and lactate production is considered a major contender. The ~33% excess CMRglucose equals 0.18 μmol glucose/g/min and predicts lactate release of 0.36 μmol/g/min. To validate such scenario, we measured the brain lactate concentration ([Lac]) in 65 children to determine if indeed lactate accumulates and is high enough to (1) account for the glucose consumed in excess of oxygen and (2) support a high rate of lactate efflux from the young brain. Across childhood, brain [Lac] was lower than predicted, and below the range for adult brain. In addition, we re-calculated the CMRglucose-CMRO2 mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 μmol/g/min, or in terms of CMRglucose, of 0.02 μmol glucose/g/min. Accumulation of [Lac] and calculated efflux of lactate from brain are not consistent with the increase in non-oxidative metabolism of glucose. In addition, the value for the lumped constant for [18F]fluorodeoxyglucose has a high impact on calculated CMRglucose and use of updated values alters or eliminates the CMRglucose-CMRO2 mismatch in developing brain. We conclude that the presently-accepted notion of non-oxidative metabolism of glucose during childhood must be revisited and deserves further investigations.

KEYWORDS:

aerobic glycolysis; bioenergetics; brain; child; development; lactate; non-oxidative metabolism

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