title: (13)C-labelled microdialysis studies of cerebral metabolism in TBI patients.
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.
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, UK. Electronic address: klc1000@wbic.cam.ac.uk.
authors.forename: Keri L H
authors.initials: KL
authors.lastname: Carpenter
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jalloh
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK; Division of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Canada.
authors.forename: Clare N
authors.initials: CN
authors.lastname: Gallagher
authors.affiliation: Department of Chemistry, University of Cambridge, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Grice
authors.affiliation: Department of Chemistry, University of Cambridge, UK.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Howe
authors.affiliation: Department of Chemistry, University of Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mason
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Timofeev
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: Adel
authors.initials: A
authors.lastname: Helmy
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, UK; Division of Anaesthesia, Department of Medicine, University of Cambridge, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kirkpatrick
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: T Adrian
authors.initials: TA
authors.lastname: Carpenter
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Canada.
authors.forename: Garnette R
authors.initials: GR
authors.lastname: Sutherland
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, UK; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hutchinson
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004734:Energy Metabolism; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D017551:Microdialysis; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D015415:Biomarkers
keywords: (13)C-labelling; Brain metabolism; Human; Microdialysis; NMR; Traumatic brain injury