title: Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations.
abstract: 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.
authors.affiliation: Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Dienel
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D019344:Lactic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid