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The effect of succi...
The effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury
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Stovell, MG (författare)
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Mada, MO (författare)
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Helmy, A (författare)
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visa fler...
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Carpenter, TA (författare)
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- Thelin, EP (författare)
- Karolinska Institutet
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Yan, JL (författare)
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Guilfoyle, MR (författare)
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Jalloh, I (författare)
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Howe, DJ (författare)
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Grice, P (författare)
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Mason, A (författare)
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Giorgi-Coll, S (författare)
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Gallagher, CN (författare)
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Murphy, MP (författare)
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Menon, DK (författare)
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Hutchinson, PJ (författare)
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Carpenter, KLH (författare)
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(creator_code:org_t)
- 2018-07-24
- 2018
- Engelska.
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11140-
- Relaterad länk:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
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- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Stovell, MG
-
Mada, MO
-
Helmy, A
-
Carpenter, TA
-
Thelin, EP
-
Yan, JL
-
visa fler...
-
Guilfoyle, MR
-
Jalloh, I
-
Howe, DJ
-
Grice, P
-
Mason, A
-
Giorgi-Coll, S
-
Gallagher, CN
-
Murphy, MP
-
Menon, DK
-
Hutchinson, PJ
-
Carpenter, KLH
-
visa färre...
- Artiklar i publikationen
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Scientific repor ...
- Av lärosätet
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Karolinska Institutet