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A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

ABSTRACT: Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-¹³C lactate metabolism in TBI with "normal" control brain and muscle, measuring ¹³C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24?h in brain, 8?h in muscle) with 8?mmol/L sodium 3-¹³C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-¹³C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p?=?0.463), with significant increases (p?=?0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate ¹³C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. ¹³C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-¹³C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited ¹³C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."

SUBMITTER: Jalloh I

PROVIDER: S-EPMC6098406 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

Jalloh Ibrahim I Helmy Adel A Howe Duncan J DJ Shannon Richard J RJ Grice Peter P Mason Andrew A Gallagher Clare N CN Murphy Michael P MP Pickard John D JD Menon David K DK Carpenter T Adrian TA Hutchinson Peter J PJ Carpenter Keri L H KLH

Journal of neurotrauma 20180518 17

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-<sup>13</sup>C lactate metabolism in TBI with "normal" control brain and muscle, measuring <sup>13</sup>C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting musc ...[more]

PMID: 29690859

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Project description:BackgroundTendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1β. It is thought that the metabolic changes play a role in tendon healing after injury.HypothesisGlucose metabolism is altered during tendon injury and healing, and modulation of this altered metabolism improves tendon repair.Study designControlled laboratory study.MethodsThe authors used the tendon injury model involving a complete incision of the Achilles tendon in C57BL/6J female mice and studied alterations of glucose metabolism in injured tendons with [U-13C]glucose and metabolomics analysis 1 and 4 weeks after surgery. They also examined the effects of dichloroacetate (DCA; an indirect lactate synthesis inhibitor) treatment on the recovery of structure and mechanical properties of injured tendons 4 weeks after surgery in the same mouse model.ResultsSignificant changes in glucose metabolism in tendons after injury surgery were detected. 13C enrichment of metabolites and intermediates, flux through glycolysis, and lactate synthesis, as well as tricarboxylic acid cycle activity, were acutely increased 1 week after injury. Increased glycolysis and lactate generation were also found 4 weeks after injury. DCA-treated injured tendons showed decreased cross-sectional area and higher values of modulus, maximum stress, and maximum force when compared with vehicle-treated injured tendons. Improved alignment of the collagen fibers was also observed in the DCA group. Furthermore, DCA treatment reduced mucoid accumulation and ectopic calcification in injured tendons.ConclusionThe findings indicate that injured tendons acutely increase glycolysis and lactate synthesis after injury and that the inhibition of lactate synthesis by DCA is beneficial for tendon healing.Clinical relevanceChanging metabolism in injured tendons may be a therapeutic target for tendon repair.

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Dataset Information

A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

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A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

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