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

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Stovell MG,Mada MO,Helmy A,Carpenter TA,Thelin EP,Yan JL,Guilfoyle MR,Jalloh I,Howe DJ,Grice P,Mason A,Giorgi-Coll S,Gallagher CN,Murphy MP,Menon DK,Hutchinson PJ,Carpenter KLH

doi

10.1038/s41598-018-29255-3

subject

Has Abstract

pub_date

2018-07-24 00:00:00

pages

11140

issue

1

issn

2045-2322

pii

10.1038/s41598-018-29255-3

journal_volume

8

pub_type

杂志文章

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