Skip Navigation


Brain Advance Access originally published online on August 20, 2009
Brain 2009 132(10):2839-2849; doi:10.1093/brain/awp202
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
132/10/2839    most recent
awp202v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gallagher, C. N.
Right arrow Articles by Hutchinson, P. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gallagher, C. N.
Right arrow Articles by Hutchinson, P. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Clare N. Gallagher1,2,*, Keri L.H. Carpenter2,3,*, Peter Grice4, Duncan J. Howe4, Andrew Mason4, Ivan Timofeev2, David K. Menon3,5, Peter J. Kirkpatrick2, John D. Pickard2,3, Garnette R. Sutherland1 and Peter J. Hutchinson2,3

1 Division of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, 1403, 29th Street NW, Calgary, Alberta T2N 2T9, Canada 2 Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK 3 Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Box 65, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK 4 Department of Chemistry, University of Cambridge, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK 5 Division of Anaesthesia, Department of Medicine, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK

Correspondence to: K.L.H. Carpenter, PhD, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK E-mail: klc1000{at}wbic.cam.ac.uk

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 13C-labelled cerebral microdialysis both to deliver 13C substrates into the brain and recover 13C metabolites from the brain, and high-resolution 13C 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 2-13C-acetate or 3-13C-lactate produced 13C 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.

Key Words: brain metabolism; 13C-labelling; microdialysis; NMR; traumatic brain injury (human)

Abbreviations: Ac, acetate; ATP, adenosine triphosphate; C, carbon; CAD, cranial access device; CNS, central nervous system; CoA, coenzyme A; CTO, craniotomy; D2O, deuterium oxide; Glc, glucose; Gln, glutamine; Glt, glutamate; Lac, lactate; NMR, nuclear magnetic resonance; p.p.m., parts per million; PPP, pentose phosphate pathway; Pyr, pyruvate; ROI, region of interest; TBI, traumatic brain injury; TCA, tricarboxylic acid

.

Received April 5, 2009. Revised June 12, 2009. Accepted June 21, 2009.

*These authors contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.