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Niklas Marklund, Kaj Blennow, Henrik Zetterberg, Elisabeth Ronne-Engström, Per Enblad, and Lars Hillered

Blumbergs PC , Scott G , Manavis J , Wainwright H , Simpson DA , McLean AJ : Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury . J Neurotrauma 12 : 565 – 572 , 1995 8 Chen SF , Richards HK , Smielewski P , Johnström P , Salvador R , Pickard JD , : Relationship between flow-metabolism uncoupling and evolving axonal injury after experimental traumatic brain injury . J Cereb Blood Flow Metab 24 : 1025 – 1036 , 2004 9 Chen XH , Siman R

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Lennart Persson and Lars Hillered

traumatic brain injury. Science 244 : 798 – 800 , 1989 Faden AI, Demediuk P, Panter SS, et al: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244: 798–800, 1989 9. Folbergrová J , MacMillan V , Siesjö BK : The effect of moderate and marked hypercapnia upon the energy state and upon the cytoplasmic NADH-NAD + ratio of the rat brain. J Neurochem 19 : 2497 – 2505 , 1972 Folbergrová J, MacMillan V, Siesjö BK: The effect of moderate and marked hypercapnia upon the

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Elisabeth Ronne-Engström, Kristina Giuliana Cesarini, Per Enblad, Göran Hesselager, Niklas Marklund, Pelle Nilsson, Konstantin Salci, Lennart Persson, and Lars Hillered

consciousness. A practical scale. Lancet 2 : 81 – 84 , 1974 Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2: 81–84, 1974 27. Vespa P , Prins M , Ronne-Engstrom E , et al : Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study. J Neurosurg 89 : 971 – 982 , 1998 Vespa P, Prins M, Ronne-Engstrom E, et al: Increase in extracellular glutamate caused by reduced

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Maria Zetterling, Lars Hillered, Per Enblad, Torbjörn Karlsson, and Elisabeth Ronne-Engström

: Effects of glucose load on brain extracellular lactate concentration in conscious rats using a microdialysis technique . Horm Metab Res 25 : 560 – 563 , 1993 23 Helbok R , Schmidt JM , Kurtz P , Hanafy KA , Fernandez L , Stuart RM , : Systemic glucose and brain energy metabolism after subarachnoid hemorrhage . Neurocrit Care 12 : 317 – 323 , 2010 24 Hillered L , Persson L , Nilsson P , Ronne-Engstrom E , Enblad P : Continuous monitoring of cerebral metabolism in traumatic brain injury: a focus on cerebral microdialysis

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Alan Hoffer and Warren R. Selman

of previous reports have examined metabolic states following traumatic brain injury. In 2006, Vespa and colleagues 7 studied energy utilization following traumatic brain injury and found significant reductions in cerebral glucose levels after intensive insulin therapy. While the global metabolic rate did not decrease, glutamate levels, the lactate/pyruvate ratio, and oxygen extraction (all markers of cellular metabolic stress) were elevated. Interestingly, no difference in the 6-month mortality rate was noted. In 20 patients with stroke or traumatic brain injury

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Mendel Castle-Kirszbaum, Scott Ayton, and Tony Goldschlager

-A , Normobaric hyperoxia in traumatic brain injury: does brain metabolic state influence the response to hyperoxic challenge? J Neurotrauma . 2011 ; 28 : 1139 – 1148 . 9 Oddo M , Levine JM , Frangos S , Brain lactate metabolism in humans with subarachnoid hemorrhage . Stroke . 2012 ; 43 : 1418 – 1421 . 10 Almeida A , Moncada S , Bolanos JP . Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway . Nat Cell Biol . 2004 ; 6 : 45 – 51 .

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Mendel Castle-Kirszbaum, Scott Ayton, and Tony Goldschlager

-A , Normobaric hyperoxia in traumatic brain injury: does brain metabolic state influence the response to hyperoxic challenge? J Neurotrauma . 2011 ; 28 : 1139 – 1148 . 9 Oddo M , Levine JM , Frangos S , Brain lactate metabolism in humans with subarachnoid hemorrhage . Stroke . 2012 ; 43 : 1418 – 1421 . 10 Almeida A , Moncada S , Bolanos JP . Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway . Nat Cell Biol . 2004 ; 6 : 45 – 51 .

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Peter Frykholm, Lars Hillered, Bengt Långström, Lennart Persson, Johann Valtysson, and Per Enblad

reliable marker of ischemia. 6, 24 Data from recent experimental and clinical microdialysis studies of traumatic brain injury indicate that valuable information on the bioenergetic status of the brain may be obtained by analyzing glucose, the primary energy substrate of the brain, alone or in combina tion with lactate, the end product of anaerobic glycolysis. 1, 2, 12, 17, 18, 20, 21, 27 In subarachnoid hemorrhage, near-zero levels of brain glucose have been interpreted as a result of complete ischemia and the occurrence of infarction. 20, 24 Results of experimental

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Carolina Samuelsson, Timothy Howells, Eva Kumlien, Per Enblad, Lars Hillered, and Elisabeth Ronne-Engström

, 1998 20 Yi JH , Hazell AS : Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury . Neurochem Int 48 : 394 – 403 , 2006

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Henrik Engquist, Anders Lewén, Lars Hillered, Elisabeth Ronne-Engström, Pelle Nilsson, Per Enblad, and Elham Rostami

a non-ischemic energy crisis (e.g., mitochondrial dysfunction). 13 In two recent studies on NIC patients with severe SAH 14 and severe traumatic brain injury (TBI), 22 cerebral ischemia was defined as an L/P ratio > 30 and pyruvate < 70 μmol/L, and cerebral mitochondrial dysfunction as an L/P ratio > 30 and pyruvate > 70 μmol/L. Based on these statements and studies, three patterns of the CMD parameters were defined to reflect the cerebral energy metabolic state of each patient in this study: normal (lactate < 4 mmol/L, L/P ratio < 30), mitochondrial