(13)C-labelled microdialysis studies of cerebral metabolism in TBI patients.

Title(13)C-labelled microdialysis studies of cerebral metabolism in TBI patients.
Publication TypeJournal Article
Year of Publication2014
AuthorsCarpenter, KLH, Jalloh, I, Gallagher, CN, Grice, P, Howe, DJ, Mason, A, Timofeev, I, Helmy, A, Murphy, MP, Menon, DK, Kirkpatrick, PJ, T Carpenter, A, Sutherland, GR, Pickard, JD, Hutchinson, PJ
JournalEur J Pharm Sci
Volume57
Pagination87-97
Date Published2014 Jun 16
ISSN1879-0720
KeywordsBiomarkers, Brain Injuries, Carbon-13 Magnetic Resonance Spectroscopy, Energy Metabolism, Humans, Mass Spectrometry, Metabolomics, Microdialysis, Predictive Value of Tests, Prognosis
Abstract

Human brain chemistry is incompletely understood and better methodologies are needed. Traumatic brain injury (TBI) causes metabolic perturbations, one result of which includes increased brain lactate levels. Attention has largely focussed on glycolysis, whereby glucose is converted to pyruvate and lactate, and is proposed to act as an energy source by feeding into neurons' tricarboxylic acid (TCA) cycle, generating ATP. Also reportedly upregulated by TBI is the pentose phosphate pathway (PPP) that does not generate ATP but produces various molecules that are putatively neuroprotective, antioxidant and reparative, in addition to lactate among the end products. We have developed a novel combination of (13)C-labelled cerebral microdialysis both to deliver (13)C-labelled substrates into brains of TBI patients and recover the (13)C-labelled metabolites, with high-resolution (13)C NMR analysis of the microdialysates. This methodology has enabled us to achieve the first direct demonstration in humans that the brain can utilise lactate via the TCA cycle. We are currently using this methodology to make the first direct comparison of glycolysis and the PPP in human brain. In this article, we consider the application of (13)C-labelled cerebral microdialysis for studying brain energy metabolism in patients. We set this methodology within the context of metabolic pathways in the brain, and (13)C research modalities addressing them.

DOI10.1016/j.ejps.2013.12.012
Alternate JournalEur J Pharm Sci
Citation Key10.1016/j.ejps.2013.12.012
PubMed ID24361470
PubMed Central IDPMC4013834
Grant ListG0600986 ID 79068 / / Medical Research Council / United Kingdom
G1002277 ID 98489 / / Medical Research Council / United Kingdom
G0001354 / / Medical Research Council / United Kingdom
G0600986 / / Medical Research Council / United Kingdom
G1002277 / / Medical Research Council / United Kingdom
/ / Canadian Institutes of Health Research / Canada
MC_U105663142 / / Medical Research Council / United Kingdom
NIHR-RP-R3-12-013 / / Department of Health / United Kingdom
G9439390 / / Medical Research Council / United Kingdom
G9439390 ID 65883 / / Medical Research Council / United Kingdom