Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood
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...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00631/full |
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| author | Helene Benveniste Gerald Dienel Gerald Dienel Zvi Jacob Hedok Lee Rany Makaryus Albert Gjedde Fahmeed Hyder Douglas L. Rothman |
| author_facet | Helene Benveniste Gerald Dienel Gerald Dienel Zvi Jacob Hedok Lee Rany Makaryus Albert Gjedde Fahmeed Hyder Douglas L. Rothman |
| author_sort | Helene Benveniste |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-14T05:17:04Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-899c36ddac5548bca7490281af7937b12022-12-21T23:15:48ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-09-011210.3389/fnins.2018.00631364107Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across ChildhoodHelene Benveniste0Gerald Dienel1Gerald Dienel2Zvi Jacob3Hedok Lee4Rany Makaryus5Albert Gjedde6Fahmeed Hyder7Douglas L. Rothman8Department of Anesthesiology, Yale School of Medicine, Yale University, New Haven, CT, United StatesDepartment of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, United StatesDepartment of Anesthesiology, Stony Brook University, Stony Brook, NY, United StatesDepartment of Anesthesiology, Yale School of Medicine, Yale University, New Haven, CT, United StatesDepartment of Anesthesiology, Stony Brook University, Stony Brook, NY, United StatesDepartment of Translational Neurobiology, University of Southern Denmark, Odense, DenmarkDepartment of Biomedical Engineering & Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, CT, United StatesDepartment of Biomedical Engineering & Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, CT, United StatesBrain 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.https://www.frontiersin.org/article/10.3389/fnins.2018.00631/fullnon-oxidative metabolismaerobic glycolysisbrainchilddevelopmentlactate |
| spellingShingle | Helene Benveniste Gerald Dienel Gerald Dienel Zvi Jacob Hedok Lee Rany Makaryus Albert Gjedde Fahmeed Hyder Douglas L. Rothman Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood Frontiers in Neuroscience non-oxidative metabolism aerobic glycolysis brain child development lactate |
| title | Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood |
| title_full | Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood |
| title_fullStr | Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood |
| title_full_unstemmed | Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood |
| title_short | Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood |
| title_sort | trajectories of brain lactate and re visited oxygen glucose index calculations do not support elevated non oxidative metabolism of glucose across childhood |
| topic | non-oxidative metabolism aerobic glycolysis brain child development lactate |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00631/full |
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