The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study

被引:163
作者
Gallagher, Clare N. [1 ,2 ]
Carpenter, Keri L. H. [1 ,3 ]
Grice, Peter [4 ]
Howe, Duncan J. [4 ]
Mason, Andrew [4 ]
Timofeev, Ivan [1 ]
Menon, David K. [3 ,5 ]
Kirkpatrick, Peter J. [1 ]
Pickard, John D. [1 ,3 ]
Sutherland, Garnette R. [2 ]
Hutchinson, Peter J. [1 ,3 ]
机构
[1] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Div Neurosurg, Cambridge CB2 0QQ, England
[2] Univ Calgary, Dept Clin Neurosci, Div Neurosurg, Calgary, AB T2N 2T9, Canada
[3] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Wolfson Brain Imaging Ctr, Cambridge CB2 0QQ, England
[4] Univ Cambridge, Univ Chem Lab, Dept Chem, Cambridge CB2 1EW, England
[5] Univ Cambridge, Addenbrookes Hosp, Dept Med, Div Anaesthesia, Cambridge CB2 0QQ, England
基金
英国医学研究理事会;
关键词
brain metabolism; C-13-labelling; microdialysis; NMR; traumatic brain injury (human); HUMAN CEREBRAL-CORTEX; GLUCOSE-METABOLISM; ENERGY-METABOLISM; AMINO-ACIDS; HEAD-INJURY; SUBARACHNOID HEMORRHAGE; GLUTAMATE RELEASE; NEURONAL-ACTIVITY; PH-DEPENDENCE; RAT-BRAIN;
D O I
10.1093/brain/awp202
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Energy metabolism in the human brain is not fully understood. Classically, glucose is regarded as the major energy substrate. However, lactate (conventionally a product of anaerobic metabolism) has been proposed to act as an energy source, yet whether this occurs in man is not known. Here we show that the human brain can indeed utilize lactate as an energy source via the tricarboxylic acid cycle. We used a novel combination of C-13-labelled cerebral microdialysis both to deliver C-13 substrates into the brain and recover C-13 metabolites from the brain, and high-resolution C-13 nuclear magnetic resonance. Microdialysis catheters were placed in the vicinity of focal lesions and in relatively less injured regions of brain, in patients with traumatic brain injury. Infusion with 2-C-13-acetate or 3-C-13-lactate produced C-13 signals for glutamine C4, C3 and C2, indicating tricarboxylic acid cycle operation followed by conversion of glutamate to glutamine. This is the first direct demonstration of brain utilization of lactate as an energy source in humans.
引用
收藏
页码:2839 / 2849
页数:11
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