The effect of succinate on brain NADH/NAD redox state and high energy phosphate metabolism in acute traumatic brain injury.

TitleThe effect of succinate on brain NADH/NAD redox state and high energy phosphate metabolism in acute traumatic brain injury.
Publication TypeJournal Article
Year of Publication2018
AuthorsStovell, MG, Mada, MO, Helmy, A, T Carpenter, A, Thelin, EP, Yan, J-L, Guilfoyle, MR, Jalloh, I, Howe, DJ, Grice, P, Mason, A, Giorgi-Coll, S, Gallagher, CN, Murphy, MP, Menon, DK, Hutchinson, PJ, Carpenter, KLH
JournalSci Rep
Volume8
Issue1
Pagination11140
Date Published2018 Jul 24
ISSN2045-2322
Abstract

A 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 P 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  0.4, 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.

DOI10.1038/s41598-018-29255-3
Alternate JournalSci Rep
Citation Key10.1038/s41598-018-29255-3
PubMed ID30042490
PubMed Central IDPMC6057963
Grant List / / Wellcome Trust / United Kingdom