Human Cerebral Perfusion, Oxygen Consumption, and Lactate Production in Response to Hypoxic Exposure
Open Access
- 27 August 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Cerebral Cortex
- Vol. 32 (6), 1295-1306
- https://doi.org/10.1093/cercor/bhab294
Abstract
Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia. A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy. CBF increased (P < 10−4), whereas the CMRO2 remained unaffected (P > 0.076) in all groups, as expected. Lactate increased in groups inhaling hypoxic air (poikilocapnic hypoxia: |$0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$|, P < 10−6; isocapnic hypoxia: |$0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$|, P = 0.003) but was unaffected by CO (P = 0.36). Lactate production was not associated with reduced CMRO2. These results point toward a mechanism of lactate production by upregulation of glycolysis mediated by sensing a reduced arterial oxygen pressure. The released lactate may act as a signaling molecule engaged in vasodilation.Funding Information
- Danish Council for Independent Research (8020-00251B)
- Rigshospitalets Forskningspulje and Lundbeck Foundation (R155-2014-171)
This publication has 72 references indexed in Scilit:
- Lactate Modulates the Activity of Primary Cortical Neurons through a Receptor-Mediated PathwayPLOS ONE, 2013
- Normal glucose uptake in the brain and heart requires an endothelial cell-specific HIF-1α–dependent functionProceedings of the National Academy of Sciences of the United States of America, 2012
- Hypoxia induces angiogenic factors in brain microvascular endothelial cellsMicrovascular Research, 2012
- Hypoxia-Inducible Factors in Physiology and MedicineCell, 2012
- Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic stateProceedings of the National Academy of Sciences of the United States of America, 2012
- Neurovascular ImagingFrontiers in Neuroenergetics, 2012
- Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapniaJournal of Cerebral Blood Flow & Metabolism, 2011
- Glial and neuronal control of brain blood flowNature, 2010
- MRI Estimation of Global Brain Oxygen Consumption RateJournal of Cerebral Blood Flow & Metabolism, 2010
- Cell–cell and intracellular lactate shuttlesJournal Of Physiology-London, 2009