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dc.contributor.authorStovell, Matthew
dc.contributor.authorMada, Marius
dc.contributor.authorHelmy, Adel
dc.contributor.authorCarpenter, Adrian
dc.contributor.authorThelin, Eric
dc.contributor.authorYan, Jiun
dc.contributor.authorGuilfoyle, Mathew
dc.contributor.authorJalloh, I
dc.contributor.authorHowe, Duncan J
dc.contributor.authorGrice, Peter
dc.contributor.authorMason, Andrew
dc.contributor.authorGiorgi-Coll, Susan
dc.contributor.authorGallagher, Clare N
dc.contributor.authorMurphy, Mike
dc.contributor.authorMenon, David
dc.contributor.authorHutchinson, Peter
dc.contributor.authorCarpenter, Keri
dc.date.accessioned2018-11-28T11:39:38Z
dc.date.available2018-11-28T11:39:38Z
dc.date.issued2018-07-24
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286016
dc.description.abstractA key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation of brain lactate/pyruvate (L/P) ratio in the absence of hypoxia. We previously showed that succinate can improve brain extracellular chemistry in acute TBI, but it was not clear if this translates to a change in downstream energy metabolism. We studied the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio (PCr/ATP)) with 31P MRS at 3T, and tissue NADH/NAD+ redox state using microdialysis (L/P ratio) in eight patients with acute major TBI (mean 7 days). Succinate perfusion was associated with increased extracellular pyruvate (+26%, p <0.0001) and decreased L/P ratio ( 13%, p <0.0001) in patients overall (baseline-vs-supplementation over time), but no clear-cut change in 31P MRS PCr/ATP in our cohort (p >0.4, supplemented voxel-vs-contralateral voxel). However, the percentage decrease in L/P ratio for each patient following succinate perfusion correlated significantly with their percentage increase in PCr/ATP ratio (Spearman's rank correlation, r =-0.86, p =0.024). Our findings support the interpretation that L/P ratio is linked to brain energy state, and that succinate may support brain energy metabolism in select TBI patients suffering from mitochondrial dysfunction.
dc.description.sponsorshipMRC Grant No. G1002277 ID98489. MRC Grant No. G0600986 ID79068. MRC, MC_U105663142. Wellcome Trust 110159/Z/15/Z. National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme. Medical Research Council Project code SRAG/071, ID RG87629. Swedish Society for Medical Research. Canadian Institute of Health Research Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship Grant no. G0802251.
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBrain injuries
dc.subjectMolecular neuroscience
dc.subjectNeurochemistry
dc.subjectTranslational research
dc.subjectTrauma
dc.titleThe effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury
dc.typeArticle
prism.number11140
prism.publicationNameScientific Reports
prism.volume8
dc.identifier.doi10.17863/CAM.33336
dcterms.dateAccepted2018-07-04
rioxxterms.versionofrecord10.1038/s41598-018-29255-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2018-07-04
dc.contributor.orcidStovell, Matthew [0000-0002-4172-4617]
dc.contributor.orcidMada, Marius [0000-0002-9903-3835]
dc.contributor.orcidHelmy, Adel [0000-0002-0531-0556]
dc.contributor.orcidCarpenter, Adrian [0000-0002-2939-8222]
dc.contributor.orcidThelin, Eric [0000-0002-2338-4364]
dc.contributor.orcidGrice, Peter [0000-0003-4658-4534]
dc.contributor.orcidGiorgi-Coll, Susan [0000-0002-9367-9408]
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.contributor.orcidMenon, David [0000-0002-3228-9692]
dc.contributor.orcidHutchinson, Peter [0000-0002-2796-1835]
dc.contributor.orcidCarpenter, Keri [0000-0001-8236-7727]
dc.identifier.eissn2045-2322
dc.publisher.urlhttps://www.nature.com/articles/s41598-018-29255-3#article-info
rioxxterms.typeJournal Article/Review
pubs.funder-project-idTCC (None)
pubs.funder-project-idMedical Research Council (G1002277)
pubs.funder-project-idMedical Research Council (G0600986)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)
pubs.funder-project-idMedical Research Council (MC_UU_00015/3)
pubs.funder-project-idMedical Research Council (MC_U105663142)
pubs.funder-project-idMedical Research Council (G0802251)
pubs.funder-project-idMedical Research Council (MR/N025792/1)
cam.issuedOnline2018-07-24
dc.identifier.urlhttps://www.nature.com/articles/s41598-018-29255-3#article-info


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International