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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.

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


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.


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

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