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- Title
The effect of succinate on brain NADH/NAD<sup>+</sup> redox state and high energy phosphate metabolism in acute traumatic brain injury.
- Authors
Stovell, Matthew G.; Mada, Marius O.; Helmy, Adel; Carpenter, T. Adrian; Thelin, Eric P.; Yan, Jiun-Lin; Guilfoyle, Mathew R.; Jalloh, Ibrahim; Howe, Duncan J.; Grice, Peter; Mason, Andrew; Giorgi-Coll, Susan; Gallagher, Clare N.; Murphy, Michael P.; Menon, David K.; Hutchinson, Peter J.; Carpenter, Keri L. H.
- 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 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 existed 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.
- Publication
Scientific Reports, 2018, Vol 8, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-018-29255-3