Cerebral Lactate Metabolism After Traumatic Brain Injury
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  • 作者:Camille Patet ; Tamarah Suys ; Laurent Carteron…
  • 关键词:Cerebral metabolism ; Energetic dysfunction ; Glucose ; Lactate ; Traumatic brain injury
  • 刊名:Current Neurology and Neuroscience Reports
  • 出版年:2016
  • 出版时间:April 2016
  • 年:2016
  • 卷:16
  • 期:4
  • 全文大小:505 KB
  • 参考文献:1.Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008;7(8):728–41. doi:10.​1016/​S1474-4422(08)70164-9 .CrossRef PubMed
    2.Rostami E, Engquist H, Enblad P. Imaging of cerebral blood flow in patients with severe traumatic brain injury in the neurointensive care. Front Neurol. 2014;5:114. doi:10.​3389/​fneur.​2014.​00114 .PubMed PubMedCentral
    3.Vespa PM, McArthur D, O'Phelan K, Glenn T, Etchepare M, Kelly D, et al. Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb Blood Flow Metab. 2003;23(7):865–77. doi:10.​1097/​01.​WCB.​0000076701.​45782.​EF .CrossRef PubMed
    4.Carre E, Ogier M, Boret H, Montcriol A, Bourdon L, Jean-Jacques R. Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg? Front Neurol. 2013;4:146. doi:10.​3389/​fneur.​2013.​00146 .CrossRef PubMed PubMedCentral
    5.Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005;25(6):763–74. doi:10.​1038/​sj.​jcbfm.​9600073 .CrossRef PubMed PubMedCentral
    6.Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A. 1994;91(22):10625–9.CrossRef PubMed PubMedCentral
    7.Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon DK, Carpenter KL, et al. Lactate uptake by the injured human brain: evidence from an arteriovenous gradient and cerebral microdialysis study. J Neurotrauma. 2013;30(24):2031–7. doi:10.​1089/​neu.​2013.​2947 .CrossRef PubMed PubMedCentral
    8.Glenn TC, Kelly DF, Boscardin WJ, McArthur DL, Vespa P, Oertel M, et al. Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. J Cereb Blood Flow Metab. 2003;23(10):1239–50. doi:10.​1097/​01.​WCB.​0000089833.​23606.​7F .CrossRef PubMed
    9.••
Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F, et al. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med. 2014;40(3):412–21. doi:10.​1007/​s00134-013-3203-6 . This recent pilot phase II investigational study examined the effect of a short infusion of hypertonic lactate in TBI patients monitored with CMD. It was found a significant and clinically relevant increase of CMD glucose, suggesting a beneficial cerebral glucose sparing-effect. Additional positive effects of hypertonic lactate were the decrease of glutamate (reduced excitotoxicity) and of ICP.CrossRef PubMed
10.Rice AC, Zsoldos R, Chen T, Wilson MS, Alessandri B, Hamm RJ, et al. Lactate administration attenuates cognitive deficits following traumatic brain injury. Brain Res. 2002;928(1–2):156–9.CrossRef PubMed
11.Holloway R, Zhou Z, Harvey HB, Levasseur JE, Rice AC, Sun D, et al. Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat. Acta Neurochir. 2007;149(9):919–27. doi:10.​1007/​s00701-007-1241-y . discussion 27.CrossRef PubMed
12.Oddo M, Schmidt JM, Carrera E, Badjatia N, Connolly ES, Presciutti M, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med. 2008;36(12):3233–8. doi:10.​1097/​CCM.​0b013e31818f4026​ .CrossRef PubMed
13.Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab. 2007;27(11):1766–91. doi:10.​1038/​sj.​jcbfm.​9600521 .CrossRef PubMed PubMedCentral
14.Felipe A, Beltrán AIA, María Paz M, Castro MA. Brain energy metabolism in health and disease. In: Contreras DCM, editor. Neuroscience—dealing with frontiers. Winchester: InTech; 2012.
15.Jalloh I, Carpenter KL, Grice P, Howe DJ, Mason A, Gallagher CN, et al. Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose. J Cereb Blood Flow Metab. 2015;35(1):111–20. doi:10.​1038/​jcbfm.​2014.​177 .CrossRef PubMed PubMedCentral
16.Siegel GJAB, Albers RW, et al. Substrates of cerebral metabolism. Basic neurochemistry: molecular, cellular and medical aspects. 6th ed. Philadelphia: Lippincott-Raven; 1999.
17.Fox PT, Raichle ME. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci U S A. 1986;83(4):1140–4.CrossRef PubMed PubMedCentral
18.Dalsgaard MK. Fuelling cerebral activity in exercising man. J Cereb Blood Flow Metab. 2006;26(6):731–50. doi:10.​1038/​sj.​jcbfm.​9600256 .CrossRef PubMed
19.Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, et al. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg. 1997;86(2):241–51. doi:10.​3171/​jns.​1997.​86.​2.​0241 .CrossRef PubMed
20.Goyal MS, Hawrylycz M, Miller JA, Snyder AZ, Raichle ME. Aerobic glycolysis in the human brain is associated with development and neotenous gene expression. Cell Metab. 2014;19(1):49–57. doi:10.​1016/​j.​cmet.​2013.​11.​020 .CrossRef PubMed PubMedCentral
21.Hutchinson PJ, O'Connell MT, Seal A, Nortje J, Timofeev I, Al-Rawi PG, et al. A combined microdialysis and FDG-PET study of glucose metabolism in head injury. Acta Neurochir. 2009;151(1):51–61. doi:10.​1007/​s00701-008-0169-1 . discussion.CrossRef PubMed
22.Carpenter KL, Jalloh I, Hutchinson PJ. Glycolysis and the significance of lactate in traumatic brain injury. Front Neurosci. 2015;9:112. doi:10.​3389/​fnins.​2015.​00112 .CrossRef PubMed PubMedCentral
23.van Hall G, Stromstad M, Rasmussen P, Jans O, Zaar M, Gam C, et al. Blood lactate is an important energy source for the human brain. J Cereb Blood Flow Metab. 2009;29(6):1121–9. doi:10.​1038/​jcbfm.​2009.​35 .CrossRef PubMed
24.Patet C, Quintard H, Suys T, Bloch J, Daniel R, Pellerin L, et al. Neuroenergetic response to prolonged cerebral glucose depletion after severe brain injury and the role of lactate. J Neurotrauma. 2015. doi:10.​1089/​neu.​2014.​3781 .
25.Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22(1):3–41. doi:10.​1089/​neu.​2005.​22.​3 .CrossRef PubMed
26.Timofeev I, Carpenter KL, Nortje J, Al-Rawi PG, O'Connell MT, Czosnyka M, et al. Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain. 2011;134(Pt 2):484–94. doi:10.​1093/​brain/​awq353 .CrossRef PubMed
27.Brooks GA, Martin NA. Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment. Front Neurosci. 2014;8:408. doi:10.​3389/​fnins.​2014.​00408 .PubMed PubMedCentral
28.Sala N, Suys T, Zerlauth JB, Bouzat P, Messerer M, Bloch J, et al. Cerebral extracellular lactate increase is predominantly nonischemic in patients with severe traumatic brain injury. J Cereb Blood Flow Metab. 2013;33(11):1815–22. doi:10.​1038/​jcbfm.​2013.​142 .CrossRef PubMed PubMedCentral
29.Gallagher CN, Carpenter KL, Grice P, Howe DJ, Mason A, Timofeev I, et al. The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. Brain. 2009;132(Pt 10):2839–49. doi:10.​1093/​brain/​awp202 .CrossRef PubMed
30.Sotelo-Hitschfeld T, Fernandez-Moncada I, Barros LF. Acute feedback control of astrocytic glycolysis by lactate. Glia. 2012;60(4):674–80. doi:10.​1002/​glia.​22304 .CrossRef PubMed
31.Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468(7321):232–43. doi:10.​1038/​nature09613 .CrossRef PubMed PubMedCentral
32.Vilchez D, Ros S, Cifuentes D, Pujadas L, Valles J, Garcia-Fojeda B, et al. Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat Neurosci. 2007;10(11):1407–13. doi:10.​1038/​nn1998 .CrossRef PubMed
33.Godoy DA, Di Napoli M, Rabinstein AA. Treating hyperglycemia in neurocritical patients: benefits and perils. Neurocrit Care. 2010;13(3):425–38. doi:10.​1007/​s12028-010-9404-8 .CrossRef PubMed
34.Benarroch EE. Glycogen metabolism: metabolic coupling between astrocytes and neurons. Neurology. 2010;74(11):919–23. doi:10.​1212/​WNL.​0b013e3181d3e44b​ .CrossRef PubMed
35.Matsui T, Soya S, Kawanaka K, Soya H. Brain glycogen decreases during intense exercise without hypoglycemia: the possible involvement of serotonin. Neurochem Res. 2015;40(7):1333–40. doi:10.​1007/​s11064-015-1594-1 .CrossRef PubMed
36.Berthet C, Castillo X, Magistretti PJ, Hirt L. New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration. Cerebrovasc Dis. 2012;34(5–6):329–35. doi:10.​1159/​000343657 .CrossRef PubMed
37.Alessandri B, Schwandt E, Kamada Y, Nagata M, Heimann A, Kempski O. The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats. J Neurotrauma. 2012;29(12):2181–91. doi:10.​1089/​neu.​2011.​2067 .CrossRef PubMed
38.Sanchez-Abarca LI, Tabernero A, Medina JM. Oligodendrocytes use lactate as a source of energy and as a precursor of lipids. Glia. 2001;36(3):321–9.CrossRef PubMed
39.Castro MA, Beltran FA, Brauchi S, Concha II. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid. J Neurochem. 2009;110(2):423–40. doi:10.​1111/​j.​1471-4159.​2009.​06151.​x .CrossRef PubMed
40.Porras OH, Ruminot I, Loaiza A, Barros LF. Na(+)-Ca(2+) cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes. Glia. 2008;56(1):59–68. doi:10.​1002/​glia.​20589 .CrossRef PubMed
41.Gladden LB. Current trends in lactate metabolism: introduction. Med Sci Sports Exerc. 2008;40(3):475–6. doi:10.​1249/​MSS.​0b013e31816154c9​ .CrossRef PubMed
42.Dusick JR, Glenn TC, Lee WN, Vespa PM, Kelly DF, Lee SM, et al. Increased pentose phosphate pathway flux after clinical traumatic brain injury: a [1,2-13C2]glucose labeling study in humans. J Cereb Blood Flow Metab. 2007;27(9):1593–602. doi:10.​1038/​sj.​jcbfm.​9600458 .CrossRef PubMed
43.Mosienko V, Teschemacher AG, Kasparov S. Is L-lactate a novel signaling molecule in the brain? J Cereb Blood Flow Metab. 2015;35(7):1069–75. doi:10.​1038/​jcbfm.​2015.​77 .CrossRef PubMed PubMedCentral
44.••
Castillo X, Rosafio K, Wyss MT, Drandarov K, Buck A, Pellerin L, et al. A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia. J Cereb Blood Flow Metab. 2015. doi:10.​1038/​jcbfm.​2015.​115 . This study perfusing isotopic D- and L-lactate on an animal model of transient focal cerebral ischemia revealed a strong neuronal expression of the HCA1 receptor in different parts of brain. They also observed a significant increase in HCA1 receptor following ischemia and reinforced by the intravenous injection of L-lactate.
45.Bozzo L, Puyal J, Chatton JY. Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway. PLoS One. 2013;8(8), e71721. doi:10.​1371/​journal.​pone.​0071721 .CrossRef PubMed PubMedCentral
46.••
Glenn TC, Martin NA, McArthur DL, Hovda DA, Vespa P, Johnson ML, et al. Endogenous nutritive support after traumatic brain injury: peripheral lactate production for glucose supply via gluconeogenesis. J Neurotrauma. 2015;32(11):811–9. doi:10.​1089/​neu.​2014.​3482 . This study extended the ANLS hypothesis to the whole body. The authors evaluated systemic lactate metabolism using isotope tracers of glucose and lactate and sampling blood from the brain through arterial and jugular bulb catheters. They determined that lactate clearance accounted for 67.1% of glucose rate of appearance in TBI patients and concluded that blood lactate is the major precursor of glucose through gluconeogenesis.CrossRef PubMed PubMedCentral
47.Sotelo-Hitschfeld T, Niemeyer MI, Machler P, Ruminot I, Lerchundi R, Wyss MT, et al. Channel-mediated lactate release by K(+)-stimulated astrocytes. J Neurosci. 2015;35(10):4168–78. doi:10.​1523/​JNEUROSCI.​5036-14.​2015 .CrossRef PubMed
48.Chen T, Qian YZ, Di X, Zhu JP, Bullock R. Evidence for lactate uptake after rat fluid percussion brain injury. Acta Neurochir Suppl. 2000;76:359–64.PubMed
49.Boumezbeur F, Petersen KF, Cline GW, Mason GF, Behar KL, Shulman GI, et al. The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J Neurosci. 2010;30(42):13983–91. doi:10.​1523/​JNEUROSCI.​2040-10.​2010 .CrossRef PubMed PubMedCentral
50.Quistorff B, Secher NH, Van Lieshout JJ. Lactate fuels the human brain during exercise. FASEB J. 2008;22(10):3443–9. doi:10.​1096/​fj.​08-106104 .CrossRef PubMed
51.Smith D, Pernet A, Hallett WA, Bingham E, Marsden PK, Amiel SA. Lactate: a preferred fuel for human brain metabolism in vivo. J Cereb Blood Flow Metab. 2003;23(6):658–64. doi:10.​1097/​01.​WCB.​0000063991.​19746.​11 .CrossRef PubMed
52.Shackford SR, Zhuang J, Schmoker J. Intravenous fluid tonicity: effect on intracranial pressure, cerebral blood flow, and cerebral oxygen delivery in focal brain injury. J Neurosurg. 1992;76(1):91–8. doi:10.​3171/​jns.​1992.​76.​1.​0091 .CrossRef PubMed
53.Duburcq T, Favory R, Mathieu D, Hubert T, Mangalaboyi J, Gmyr V, et al. Hypertonic sodium lactate improves fluid balance and hemodynamics in porcine endotoxic shock. Crit Care. 2014;18(4):467. doi:10.​1186/​s13054-014-0467-3 .CrossRef PubMed PubMedCentral
54.Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C, et al. Sodium lactate versus mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med. 2009;35(3):471–9. doi:10.​1007/​s00134-008-1283-5 .CrossRef PubMed
55.Ichai C, Payen JF, Orban JC, Quintard H, Roth H, Legrand R, et al. Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial. Intensive Care Med. 2013;39(8):1413–22. doi:10.​1007/​s00134-013-2978-9 .CrossRef PubMed
56.Glenn TC, Martin NA, Horning MA, McArthur DL, Hovda DA, Vespa P, et al. Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects. J Neurotrauma. 2015;32(11):820–32. doi:10.​1089/​neu.​2014.​3483 .CrossRef PubMed PubMedCentral
  • 作者单位:Camille Patet (1)
    Tamarah Suys (1)
    Laurent Carteron (1)
    Mauro Oddo (1)

    1. Neuroscience Critical Care Research Group, Department of Intensive Care Medicine, CHUV - Lausanne University Hospital, Rue du Bugnon 46, BH 08.623, 1011, Lausanne, Switzerland
  • 刊物主题:Neurology; Neurosciences;
  • 出版者:Springer US
  • ISSN:1534-6293
  • 文摘
    Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a “cerebral glucose-sparing effect,” and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome.

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