Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain

Bouzat, Pierre; Sala, Nathalie; Suys, Tamarah; Zerlauth, Jean-Baptiste; Marques‐Vidal, Pedro; Feihl, François; Bloch, Jocelyne; Messerer, Mahmoud; Levivier, Marc; Meuli, Reto; Magistretti, Pierre J.; Oddo, Mauro

doi:10.1007/s00134-013-3203-6

Cited by 161 publications

(165 citation statements)

References 35 publications

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“…In comparison to our findings in CSF, Bouzat et al, 201416 demonstrated that hypertonic infusion of lactate in severe TBI patients improved metabolic profile and decreased glutamate levels in the brain extracellular microdyalisate. In addition, a previous study in severe TBI patients showed that brain glucose availability decreases locally and lactate increases in the absence of ischemia.…”

Section: Discussioncontrasting

confidence: 55%

“…Based on this concept, one could argue that increased extracellular brain lactate concentrations after TBI may reflect increased astrocytic metabolic responsiveness to high glutamate concentrations. This mechanism seems to be important for the survival of severe TBI patients since hypertonic sodium lactate infusion improves ICP, hemodynamic, and energetic parameters16, 17, whereas disturbances in this metabolic coupling are associated with worse prognosis 18…”

Section: Introductionmentioning

confidence: 99%

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Elevated glutamate and lactate predict brain death after severe head trauma

Stefani

Modkovski

Hansel

et al. 2017

Ann Clin Transl Neurol

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ObjectiveClinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome.MethodsThis cross‐sectional study was carried out in a total of 20 consecutive patients (mean [SD] age, 29 [13] years; M/F, 9:1) with severe TBI Glasgow Coma Scale ≤ 8 and abnormal computed tomography scan on admission. Patients were submitted to ventricular drainage and had CSF collected between 2 and 4 h after hospital admission. Patients were then stratified according to two clinical outcomes: deterioration to brain death (nonsurvival, n = 6) or survival (survival, n = 14), within 3 days after hospital admission. CSF levels of brain‐derived substances were compared between nonsurvival and survival groups. Clinical and neurological parameters were also assessed.ResultsGlutamate and lactate are significantly increased in nonsurvival relative to survival patients. We tested the accuracy of both biomarkers to discriminate patient outcome. Setting a cutoff of >57.75, glutamate provides 80.0% of sensitivity and 84.62% of specificity (AUC: 0.8214, 95% CL: 54.55–98.08%; and a cutoff of >4.65, lactate has 100% of sensitivity and 85.71% of specificity (AUC: 0.8810, 95% CL: 54.55–98.08%). BDNF and GDNF did not discriminate poor outcome.InterpretationThis early study suggests that glutamate and lactate concentrations at hospital admission accurately predict death within 3 days after severe TBI.

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Section: Discussioncontrasting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Elevated glutamate and lactate predict brain death after severe head trauma

Stefani

Modkovski

Hansel

et al. 2017

Ann Clin Transl Neurol

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“…35 Figure 2A) predicts (i) metabolic compartmentation during brain activation coupled with glutamate-glutamine cycling, i.e., glutamate-evoked glycolysis to fuel Na + extrusion from astrocytes ( Figure 2C), lactate transfer to neurons, and neuronal lactate oxidation, with little or no rise in neuronal glycolysis; (ii) the rise in CMR O2 should stoichiometrically match the increase in CMR glc if lactate is locally oxidized; and (iii) metabolic assays of oxidative metabolism with labeled glucose or oxygen during activation should have a magnitude similar to assays of the hexokinase step using deoxyglucose (DG) (i.e., no loss of labeled lactate, which causes underestimation of calculated CMR glc and reduces CMR O2 owing to the substrate efflux). Recent reviews of this model by proponents 35,38,[41][42][43][44] do not adequately present its shortcomings, and many studies selectively cited in these reviews to support the model are not representative of similar studies in the neurometabolic literature. 45 Discordance between cited ANL-supportive studies and relevant uncited literature requires a more balanced presentation.…”

Section: Lactate As Neuronal Fuel: Astrocyte-to-neuron Lactate Shuttlementioning

confidence: 99%

“…These issues must be evaluated before implementing lactate therapies. (v) The LPR is stated 38 to be a 'marker of cerebral energy demand' but this is not accurate because LPR can change owing to the altered fluxes in ATP-producing pathways. Assume CMR glc after TBI is 0.2 μmol/g per minute, with 2ATP/ mol glucose from glycolysis and 30 from oxidation, giving rates of 0.4 and 6 μmol ATP/g per minute.…”

Section: Lactate As Supplemental Oxidative Fuel After Traumatic Brainmentioning

confidence: 99%

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Dienel

2014

J Cereb Blood Flow Metab

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Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as 'preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte-neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted.

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“…Dear Editor, In their study Bouzat et al [1] conclude that following traumatic brain injury lactate may be used by the brain as a preferential energy substrate and that intravenous infusion of hypertonic sodium lactate had positive effects on cerebral energy metabolism and intracranial pressure (ICP). The biochemical conclusions are based on data obtained from microdialysis (MD) indicating that the therapy increased the intracerebral levels of glucose and pyruvate while glutamate and ICP decreased.…”

mentioning

confidence: 99%