Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy

Frontiers in Neuroenergetics

Volumn 5, Issue OCT, 2013, Pages

  Bartnik Olson, Brenda L ^a   Harris, Neil G ^b   Shijo, Katsunori ^b   Sutton, Richard L ^b  

^a LOMA LINDA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Acetate; Glucose; Glutamate glutamine cycle; Magnetic resonance spectroscopy; Neuroglial compartmentation; Oxidative metabolism; Pentose phosphate pathway

Indexed keywords

ACETIC ACID; CARBON 13; GLUCOSE; GLUTAMIC ACID; GLUTAMINE; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; LACTIC ACID; PYRUVATE DEHYDROGENASE;

AEROBIC METABOLISM; ASTROCYTE; BRAIN METABOLISM; CARBON NUCLEAR MAGNETIC RESONANCE; CELL COMPARTMENTALIZATION; CELL METABOLISM; ENERGY METABOLISM; EXPERIMENTAL MODEL; GLIA; GLUCOSE METABOLISM; GLYCOLYSIS; HUMAN; INJURY SEVERITY; NEUROTRANSMISSION; NITROSATIVE STRESS; NONHUMAN; OXIDATION REDUCTION STATE; PENTOSE PHOSPHATE CYCLE; SHORT SURVEY; SYSTEMATIC REVIEW; TRAUMATIC BRAIN INJURY;

EID: 84904741500     PISSN: None     EISSN: 16626427     Source Type: Journal    
DOI: 10.3389/fnene.2013.00008     Document Type: Short Survey

References (125)

1. Aoyama, N., Lee, S. M., Moro, N., Hovda, D. A., and Sutton, R. L. (2008). Duration of ATP reduction affects extent of CA1 cell death in rat models of fluid percussion injury combined with secondary ischemia. Brain Res. 1230, 310-319. doi: 10.1016/j.brainres.2008.07.006
2. Arun, P., Ariyannur, P. S., Moffett, J. R., Xing, G., Hamilton, K., Grunberg, N. E., et al. (2010). Metabolic acetate therapy for the treatment of traumatic brain injury. J. Neurotrauma 27, 293-298. doi: 10.1089/neu.2009.0994
3. Arundine, M., Aarts, M., Lau, A., and Tymianski, M. (2004). Vulnerability of central neurons to secondary insults after in vitro mechanical stretch. J. Neurosci. 24, 8106-8123. doi: 10.1523/JNEUROSCI.1362-04.2004
4. Aureli, T., Di Cocco, M. E., Calvani, M., and Conti, F. (1997). The entry of [1-13C] glucose into biochemical pathways reveals a complex compartmentation and metabolite trafficking between glia and neurons: a study by 13C-NMR spectroscopy. Brain Res. 765, 218-227. doi: 10.1016/S0006-8993(97)00514-3
5. Bachelard, H. S., and Badar-Goffer, R. S. (1993). NMR spectroscopy in neurochemistry. J. Neurochem. 61, L412-L429. doi: 10.1111/j.1471-4159.1993.tb02141.x
6. Badar-Goffer, R. S., Bachelard, H. S., and Morris, P. G. (1990). Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain. Biochem. J. 266, 133-139.
7. Bambrick, L., Kristian, T., and Fiskum, G. (2004). Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection. Neurochem. Res. 29, 601-608. doi: 10.1023/B:NERE.0000014830.06376.e6
8. Baquer, N. Z., Hothersall, J. S., and McLean, P. (1988). Function and regulation of the pentose phosphate pathway in brain. Curr. Top. Cell. Regul. 29, 265-289.
9. Bartnik, B. L., Lee, S. M., Hovda, D. A., and Sutton, R. L. (2007). The fate of glucose during the period of decreased metabolism after fluid percussion injury: a 13C NMR study. J. Neurotrauma 24, 1079-1092. doi: 10.1089/neu.2006.0210
10. Bartnik, B. L., Sutton, R. L., Fukushima, M., Harris, N. G., Hovda, D. A., and Lee, S. M. (2005). Upregulation of pentose phosphate pathway and preservation of tricarboxylic acid cycle flux after experimental brain injury. J. Neurotrauma 22, 1052-1065. doi: 10.1089/neu.2005.22.1052
11. Bartnik-Olson, B. L., Oyoyo, U., Hovda, D., and Sutton, R. L. (2010). Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats. J. Neurotrauma 27, 2191-2202. doi: 10.1089/neu.2010.1508
12. Bergsneider, M., Hovda, D. A., Lee, S. M., Kelly, D. F., McArthur, D. L., Vespa, P. M., et al. (2000). Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J. Neurotrauma 17, 389-401. doi: 10.1089/neu.2000.17.389
13. Bergsneider, M., Hovda, D. A., McArthur, D. L., Etchepare, M., Huang, S.-C., Sehati, N., et al. (2001). Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability. J. Head Trauma Rehabil. 16, 135-148. doi: 10.1097/00001199-200104000-00004
14. Bergsneider, M., Hovda, D. A., Shalmon, E., Kelly, D. F., Vespa, P. M., Martin, N. A., et al. (1997). Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J. Neurosurg. 86, 241-251. doi: 10.3171/jns.1997.86.2.0241
15. Beschorner, R., Dietz, K., Schauer, N., Mittelbronn, M., Schluesener, H. J., Trautmann, K., et al. (2007). Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury. Histol. Histopathol. 22, 515-526.
16. Besson, V. C. (2009). Drug targets for traumatic brain injury from poly(ADP-ribose)polymerase pathway modulation. Br. J. Pharmacol. 157, 695-704. doi: 10.1111/j.1476-5381.2009.00229.x
17. Bourke, R. S., Kimelberg, H. K., Nelson, L. R., Barron, K. D., Auen, E. L., Popp, A. J., et al. (1980). Biology of glial swelling in experimental brain edema. Adv. Neurol. 28, 99-109.
18. Bouzier-Sore, A. K., Merle, M., Magistretti, P. J., and Pellerin, L. (2002). Feeding active neurons: (re)emergence of a nursing role for astrocytes. J. Physiol. Paris 96, 273-282. doi: 10.1016/S0928-4257(02)00016-5
19. Brekke, E. M., Walls, A. B., Schousboe, A., Waagepetersen, H. S., and Sonnewald, U. (2012). Quantitative importance of the pentose phosphate pathway determined by incorporation of (13)C from [2-(13)C]- and [3-(13)C]glucose into TCA cycle intermediates and neurotransmitter amino acids in functionally intact neurons. J. Cereb. Blood Flow Metab. 32, 1788-1799. doi: 10.1038/jcbfm.2012.85
20. Castejón, O. J. (1998). Morphological astrocytic changes in complicated human brain trauma. A light and electron microscopic study. Brain Inj. 12, 409-427. doi: 10.1080/026990598122539
21. Cerdan, S., Rodrigues, T. B., Sierra, A., Benito, M., Fonseca, L. L., Fonseca, C. P., et al. (2006). The redox switch/redox coupling hypothesis. Neurochem. Int. 48, 523-530. doi: 10.1016/j.neuint.2005.12.036
22. Cernak, I. (2005). Animal models of head trauma. NeuroRx. 2, 410-422. doi: 10.1602/neurorx.2.3.410
23. Chen, T., Qian, Y. Z., Di, X., Rice, A., Zhu, J. P., and Bullock, R. (2000). Lactate/glucose dynamics after rat fluid percussion brain injury. J. Neurotrauma 17, 135-142. doi: 10.1089/neu.2000.17.135
24. Clark, R. S., Vagni, V. A., Nathaniel, P. D., Jenkins, L. W., Dixon, C. E., and Szabo, C. (2007). Local administration of the poly(ADP-ribose) polymerase inhibitor INO-1001 prevents NAD+ depletion and improves water maze performance after traumatic brain injury in mice. J. Neurotrauma 24, 1399-1405. doi: 10.1089/neu.2007.0305
25. Clark, R. S. B., Chen, M., Kochanek, P. M., Watkins, S. C., Jin, K. L., Draviam, R., et al. (2001). Detection of single- and double-strand DNA breaks after traumatic brain injury in rats: comparison of in situ labeling techniques using DNA polymerase I, the Klenow fragment of DNA polymerase I, and terminal deoxynucleotidyl transferase. J. Neurotrauma 18, 675-689. doi: 10.1089/089771501750357627
26. Clausen, F., Hillered, L., and Gustafsson, J. (2011). Cerebral glucose metabolism after traumatic brain injury in the rat studied by 13C-glucose and microdialysis. Acta Neurochir.(Wien.) 153, 653-658. doi: 10.1007/s00701-010-0871-7
27. Cortez, S. C., McIntosh, T. K., and Noble, L. J. (1989). Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res. 482, 271-282. doi: 10.1016/0006-8993(89)91190-6
28. Cruz, F., Scott, S. R., Barroso, I., Santisteban, P., and Cerdan, S. (1998). Ontogeny and cellular localization of the pyruvate recycling system in rat brain. J. Neurochem. 70, 2613-2619. doi: 10.1046/j.1471-4159.1998.70062613.x
29. Cruz, F., and Cerdan, S. (1999). Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. NMR Biomed. 12, 451-462. doi: 10.1002/(SICI)1099-1492(199911)12:7<451::AID-NBM571>3.3.CO;2-5
30. Deelchand, D. K., Shestov, A. A., Koski, D. M., Ugurbil, K., and Henry, P. G. (2009). Acetate transport and utilization in the rat brain. J. Neurochem. 109, 46-54. doi: 10.1111/j.1471-4159.2009.05895.x
31. Dugan, L. L., Sensi, S. L., Canzoniero, L. M., Handran, S. D., Rothman, S. M., Lin, T. S., et al. (1995). Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. J. Neurosci. 15, 6377-6388.
32. Dusick, J. R., Glenn, T. C., Lee, W. N., Vespa, P. M., Kelly, D. F., Lee, S. M., et al. (2007). Increased pentose phosphate pathway flux after clinical traumatic brain injury: a [1,2-(13)C(2)]glucose labeling study in humans. J. Cereb. Blood Flow Metab. 27, 1593-1602. doi: 10.1038/sj.jcbfm.9600458
33. Fineman, I., Hovda, D. A., Smith, M., Yoshino, A., and Becker, D. P. (1993). Concussive brain injury is associated with a prolonged accumulation of calcium: a 45 Ca autoradiographic study. Brain Res. 624, 94-102. doi: 10.1016/0006-8993(93)90064-T
34. Fukushima, M., Lee, S. M., Moro, N., Hovda, D. A., and Sutton, R. L. (2009). Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury. J. Neurotrauma 26, 1095-1110. doi: 10.1089/neu.2008.0771
35. Gallagher, C. N., Carpenter, K. L., Grice, P., Howe, D. J., Mason, A., Timofeev, I., et al. (2009). The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. Brain 132, 2839-2849. doi: 10.1093/brain/awp202
36. Garcia-Nogales, P., Almeida, A., and Bolanos, J. P. (2003). Peroxynitrite protects neurons against nitric oxide-mediated apoptosis. A key role for glucose-6-phosphate dehydrogenase activity in neuroprotection. J. Biol. Chem. 278, 864-874. doi: 10.1074/jbc.M206835200
37. Grant, C. M. (2008). Metabolic reconfiguration is a regulated response to oxidative stress. J. Biol. 7, 1. doi: 10.1186/jbiol63
38. Gunter, T. E., Gunter, K. K., Sheu, S. S., and Gavin, C. E. (1994). Mitochondrial calcium transport: physiological and pathological relevance. Am. J. Physiol. 267, C313-C339.
39. Haberg, A., Qu, H., Haraldseth, O., Unsgard, G., and Sonnewald, U. (1998). In vivo injection of [1-13C]glucose and [1,2-13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat. J. Cereb. Blood Flow Metab. 18, 1223-1232. doi: 10.1097/00004647-199811000-00008
40. Hall, E. D., Andrus, P. K., and Yonkers, P. A. (1993). Brain hydroxyl radical generation in acute experimental head injury. J. Neurochem. 60, 588-594. doi: 10.1111/j.1471-4159.1993.tb03189.x
41. Hall, E. D., Bryant, Y. D., Cho, W., and Sullivan, P. G. (2008). Evolution of post-traumatic neurodegeneration after controlled cortical impact traumatic brain injury in mice and rats as assessed by the de olmos silver and fluorojade staining methods. J. Neurotrauma 25, 235-247. doi: 10.1089/neu.2007.0383
42. Hassel, B., Sonnewald, U., and Fonnum, F. (1995). Glial-neuronal interactions as studied by cerebral metabolism of [2-13C]acetate and [1-13C]glucose: an ex vivo 13C NMR spectroscopic study. J. Neurochem. 64, 2773-2782. doi: 10.1046/j.1471-4159.1995.64062773.x
43. Hassel, B., and Sonnewald, U. (1995). Glial formation of pyruvate and lactate from TCA cycle intermediates: implications for the inactivation of transmitter amino acids. J. Neurochem. 65, 2227-2234. doi: 10.1046/j.1471-4159.1995.65052227.x
44. Hertz, L. (2003). Astrocytic amino acid metabolism under control conditions and during oxygen and/or glucose deprivation. Neurochem. Res. 28, 243-258. doi: 10.1023/A:1022377100379
45. Hothersall, J. S., Greenbaum, A. L., and McLean, P. (1982). The functional significance of the pentose phosphate pathway in synaptosomes: protection against peroxidative damage by catecholamines and oxidants. J. Neurochem. 39, 1325-1332. doi: 10.1111/j.1471-4159.1982.tb12574.x
46. Hovda, D. A. (1996). "Metabolic dysfunction," in Neurotrauma, eds R. K.Narayan, J. E. Wilberger, and J. T. Povlishock (New York, NY: McGraw-Hill, Inc.), 1459-1478.
47. Hovda, D. A., Yoshino, A., Kawamata, T., Katayama, Y., and Becker, D. P. (1991). Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study. Brain Res. 567, 1-10. doi: 10.1016/0006-8993(91)91429-5
48. Inao, S., Marmarou, A., Clarke, G. D., Andersen, B. J., Fatouros, P. P., and Young, H. F. (1988). Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury. J. Neurosurg. 69, 736-744. doi: 10.3171/jns.1988.69.5.0736
49. Ip, E. Y., Zanier, E. R., Moore, A. H., Lee, S. M., and Hovda, D. A. (2003). Metabolic, neurochemical, and histologic responses to vibrissa motor cortex stimulation after traumatic brain injury. J. Cereb. Blood Flow Metab. 23, 900-910. doi: 10.1097/01.WCB.0000076702.71231.F2
50. Jiang, X. B., Ohno, K., Qian, L., Tominaga, B., Kuroiwa, T., Nariai, T., et al. (2000). Changes in local cerebral blood flow, glucose utilization, and mitochondrial function following traumatic brain injury in rats. Neurol. Med. Chir. (Tokyo) 40, 16-28. doi: 10.2176/nmc.40.16
51. Jolivet, R., Allaman, I., Pellerin, L., Magistretti, P. J., and Weber, B. (2010). Comment on recent modeling studies of astrocyte-neuron metabolic interactions. J. Cereb. Blood Flow Metab. 30, 1982-1986. doi: 10.1038/jcbfm.2010.132
52. Katayama, Y., Becker, D. P., Tamura, T., and Hovda, D. A. (1990). Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg. 73, 889-900. doi: 10.3171/jns.1990.73.6.0889
53. Kauppinen, T. M. (2007). Multiple roles for poly(ADP-ribose)polymerase-1 in neurological disease. Neurochem. Int. 50, 954-958. doi: 10.1016/j.neuint.2006.11.010
54. Kawamata, T., Katayama, Y., Hovda, D. A., Yoshino, A., and Becker, D. P. (1995). Lactate accumulation following concussive brain injury: the role of ionic fluxs induced by excitatory amino acids. Brain Res. 674, 196-204. doi: 10.1016/0006-8993(94)01444-M
55. Kelly, D. F., Kozlowski, D. A., Haddad, E., Echiverri, A., Hovda, D. A., and Lee, S. M. (2000). Ethanol reduces metabolic uncoupling following experimental head injury. J. Neurotrauma 17, 261-272. doi: 10.1089/neu.2000.17.261
56. Kilbaugh, T. J., Bhandare, S., Lorom, D. H., Saraswati, M., Robertson, C. L., and Margulies, S. S. (2011). Cyclosporin a preserves mitochondrial function after traumatic brain injury in the immature rat and piglet. J. Neurotrauma 28, 763-774. doi: 10.1089/neu.2010.1635
57. Komjati, K., Besson, V. C., and Szabo, C. (2005). Poly (adp-ribose) polymerase inhibitors as potential therapeutic agents in stroke and neurotrauma. Curr. Drug Targets CNS Neurol. Disord. 4, 179-194. doi: 10.2174/1568007053544138
58. Lai, Y., Chen, Y., Watkins, S. C., Nathaniel, P. D., Guo, F., Kochanek, P. M., et al. (2008). Identification of poly-ADP-ribosylated mitochondrial proteins after traumatic brain injury. J. Neurochem. 104, 1700-1711. doi: 10.1111/j.1471-4159.2007.05114.x
59. Laird, M. D., Vender, J. R., and Dhandapani, K. M. (2008). Opposing roles for reactive astrocytes following traumatic brain injury. Neurosignals 16, 154-164. doi: 10.1159/000111560
60. Langfitt, T. W., Obrist, W. D., Alavi, A., Grossman, R. I., Zimmerman, R., Jaggi, J., et al. (1986). Computerized tomography, magnetic resonance imaging, and positron emission tomography in the study of brain trauma. Preliminary observations. J. Neurosurg. 64, 760-767. doi: 10.3171/jns.1986.64.5.0760
61. Laplaca, M. C., Raghupathi, R., Verma, A., Pieper, A. A., Saatman, K. E., Snyder, S. H., et al. (1999). Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat. J. Neurochem. 73, 205-213. doi: 10.1046/j.1471-4159.1999.0730205.x
62. Laplaca, M. C., Zhang, J., Raghupathi, R., Li, J. H., Smith, F., Bareyre, F. M., et al. (2001). Pharmacologic inhibition of poly(ADP-ribose) polymerase is neuroprotective following traumatic brain injury in rats. J. Neurotrauma 18, 369-376. doi: 10.1089/089771501750170912
63. Lebon, V., Petersen, K. F., Cline, G. W., Shen, J., Mason, G. F., Dufour, S., et al. (2002). Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J. Neurosci. 22, 1523-1531.
64. Lee, S. M., Wong, D. A., Samii, A., and Hovda, D. A. (1999). Evidence for energy failure following irreversible traumatic brain injury. Ann. N.Y. Acad. Sci. 893, 337-340. doi: 10.1111/j.1749-6632.1999.tb07849.x
65. Lee, W. N., Boros, L. G., Puigjaner, J., Bassilian, S., Lim, S., and Cascante, M. (1998). Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2-13C2]glucose. Am. J. Physiol. 274, E843-E851.
66. Lewen, A., and Hillered, L. (1998). Involvement of reactive oxygen species in membrane phospholipid breakdown and energy perturbation after traumatic brain injury in the rat. J. Neurotrauma 15, 521-530. doi: 10.1089/neu.1998.15.521
67. Magistretti, P. J., and Pellerin, L. (1999). Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 354, 1155-1163. doi: 10.1098/rstb.1999.0471
68. Mangia, S., DiNuzzo, M., Giove, F., Carruthers, A., Simpson, I. A., and Vannucci, S. J. (2011). Response to 'comment on recent modeling studies of astrocyte-neuron metabolic interactions': much ado about nothing. J. Cereb. Blood Flow Metab. 31, 1346-1353. doi: 10.1038/jcbfm.2011.29
69. Marcoux, J., McArthur, D. A., Miller, C., Glenn, T. C., Villablanca, P., Martin, N. A., et al. (2008). Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury. Crit. Care Med. 36, 2871-2877. doi: 10.1097/CCM.0b013e318186a4a0
70. Marklund, N., Clausen, F., Ander, T. L., and Hillered, L. (2001). Monitoring of reactive oxygen species production after traumatic brain injury in rats with microdialysis and the 4-hydroxybenzoic acid trapping method. J. Neurotrauma 18, 1217-1227. doi: 10.1089/089771501317095250
71. McKenna, M. C. (2007). The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J. Neurosci. Res. 85, 3347-3358. doi: 10.1002/jnr.21444
72. McKenna, M. C., Sonnewald, U., Huang, X., Stevenson, J., and Zielke, H. R. (1996). Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J. Neurochem. 66, 386-393. doi: 10.1046/j.1471-4159.1996.66010386.x
73. McKenna, M. C., Waagepetersen, H. S., Schousboe, A., and Sonnewald, U. (2006). Neuronal and Astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents current evidence and pharmacological tools. Biochem. Pharmacol. 71, 399-407. doi: 10.1016/j.bcp.2005.10.011
74. Mendez, D. R., Cherian, L., Moore, N., Arora, T., Liu, P. K., and Roberstson, C. S. (2004). Oxidative DNA lesions in a rodent model of traumatic brain injury. J. Trauma 56, 1235-1240. doi: 10.1097/01.TA.0000130759.62286.0E
75. Moore, A. H., Osteen, C. L., Chatziioannou, A. F., Hovda, D. A., and Cherry, S. R. (2000). Quantitative assessment of longitudinal metabolic changes in vivo after traumatic brain injury in the adult rat using FDG-microPET. J. Cereb. Blood Flow Metab. 20, 1492-1501. doi: 10.1097/00004647-200010000-00011
76. Moro, N., Ghavim, S., Hovda, D. A., and Sutton, R. L. (2011). Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury. Neurosci. Lett. 491, 158-162. doi: 10.1016/j.neulet.2011.01.029
77. Moro, N., and Sutton, R. L. (2010). Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat. Exp. Neurol. 225, 391-401. doi: 10.1016/j.expneurol.2010.07.013
78. Mustafa, A. G., Singh, I. N., Wang, J., Carrico, K. M., and Hall, E. D. (2010). Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl radicals. J. Neurochem. 114, 271-280. doi: 10.1111/j.1471-4159.2010.06749.x
79. Myer, D. J., Gurkoff, G. G., Lee, S. M., Hovda, D. A., and Sofroniew, M. V. (2006). Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129, 2761-2772. doi: 10.1093/brain/awl165
80. Nilsson, P., Hillered, L., Ponten, U., and Ungerstedt, U. (1990). Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J. Cereb. Blood Flow Metab. 10, 631-637. doi: 10.1038/jcbfm.1990.115
81. Opii, W. O., Nukala, V. N., Sultana, R., Pandya, J. D., Day, K. M., Merchant, M. L., et al. (2007). Proteomic identification of oxidized mitochondrial proteins following experimental traumatic brain injury. J. Neurotrauma 24, 772-789. doi: 10.1089/neu.2006.0229
82. Osteen, C. L., Moore, A. H., Prins, M. L., and Hovda, D. A. (2001). Age-dependency of 45 calcium accumulation following lateral fluid percussion: acute and delayed patterns. J. Neurotrauma 18, 141-162. doi: 10.1089/08977150150502587
83. Parkin, M., Hopwood, S., Jones, D. A., Hashemi, P., Landolt, H., Fabricius, M., et al. (2005). Dynamic changes in brain glucose and lactate in pericontusional areas of the human cerebral cortex, monitored with rapid sampling on-line microdialysis: relationship with depolarisation-like events. J. Cereb. Blood Flow Metab. 25, 402-413. doi: 10.1038/sj.jcbfm.9600051
84. Pascual, J. M., Carceller, F., Roda, J. M., and Cerdan, S. (1998). Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats. Stroke 29, 1048-1056. doi: 10.1161/01.STR.29.5.1048
85. Pellerin, L., Bouzier-Sore, A. K., Aubert, A., Serres, S., Merle, M., Costalat, R., et al. (2007). Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55, 1251-1262. doi: 10.1002/glia.20528
86. Peng, L., Gu, L., Zhang, H., Huang, X., Hertz, E., and Hertz, L. (2007). Glutamine as an energy substrate in cultured neurons during glucose deprivation. J. Neurosci. Res. 85, 3480-3486. doi: 10.1002/jnr.21262
87. Prins, M. L., and Hovda, D. A. (2001). Mapping cerebral glucose metabolism during spatial learning: interactions of development and traumatic brain injury. J. Neurotrauma 18, 31-46. doi: 10.1089/089771501750055758
88. Ralser, M., Wamelink, M. M., Kowald, A., Gerisch, B., Heeren, G., Struys, E. A., et al. (2007). Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J. Biol. 6, 10. doi: 10.1186/jbiol61
89. Ramonet, D., Rodriguez, M. J., Fredriksson, K., Bernal, F., and Mahy, N. (2004). In vivo neuroprotective adaptation of the glutamate/glutamine cycle to neuronal death. Hippocampus 14, 586-594. doi: 10.1002/hipo.10188
90. Rao, V. L., Baskaya, M. K., Dogan, A., Rothstein, J. D., and Dempsey, R. J. (1998). Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain. J. Neurochem. 70, 2020-2027. doi: 10.1046/j.1471-4159.1998.70052020.x
91. Rao, V. L., Dogan, A., Bowen, K. K., Todd, K. G., and Dempsey, R. J. (2001). Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain. Eur. J. Neurosci. 13, 119-128. doi: 10.1046/j.1460-9568.2001.01367.x
92. Readnower, R. D., Pandya, J. D., McEwen, M. L., Pauly, J. R., Springer, J. E., and Sullivan, P. G. (2011). Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats. J. Neurotrauma 28, 1845-1853. doi: 10.1089/neu.2011.1755
93. Rose, M. E., Huerbin, M. B., Melick, J., Marion, D. W., Palmer, A. M., Schiding, J. K., et al. (2002). Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury. Brain Res. 935, 40-46. doi: 10.1016/S0006-8993(02)02445-9
94. Satchell, M. A., Zhang, X., Kochanek, P. M., Dixon, C. E., Jenkins, L. W., Melick, J., et al. (2003). A dual role for poly-ADP-ribosylation in spatial memory acquisition after traumatic brain injury in mice involving NAD+ depletion and ribosylation of 14-13-3gamma. J. Neurochem. 85, 697-708. doi: 10.1046/j.1471-4159.2003.01707.x
95. Scafidi, S., O'Brien, J., Hopkins, I., Robertson, C., Fiskum, G., and McKenna, M. (2009). Delayed cerebral oxidative glucose metabolism after traumatic brain injury in young rats. J. Neurochem. 109(Suppl. 1), 189-197. doi: 10.1111/j.1471-4159.2009.05896.x
96. Schinder, A. F., Olson, E. C., Spitzer, N. C., and Montal, M. (1996). Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J. Neurosci. 16, 6125-6133.
97. Schrader, M. C., Eskey, C. J., Simplaceanu, V., and Ho, C. (1993). A carbon-13 nuclear magnetic resonance investigation of the metabolic fluxes associated with glucose metabolism in human erythrocytes. Biochim. Biophys. Acta 1182, 162-178. doi: 10.1016/0925-4439(93)90138-Q
98. Schousboe, A., Westergaard, N., Waagepetersen, H. S., Larsson, O. M., Bakken, I. J., and Sonnewald, U. (1997). Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Glia 21, 99-105. doi: 10.1002/(SICI)1098-1136(199709)21:1<99::AID-GLIA11>3.0.CO;2-W
99. Shank, R. P., Leo, G. C., and Zilkha, E. (1993). Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D- [1-13C] glucose metabolism. J. Neurochem. 61, 315-323. doi: 10.1111/j.1471-4159.1993.tb03570.x
100. Shank, R. P., Bennett, G. S., Freytag, S. O., and Campbell, G. L. (1985). Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 329, 364-367. doi: 10.1016/0006-8993(85)90552-9
101. Sharma, P., Benford, B., Li, Z. Z., and Ling, G. S. (2009). Role of pyruvate dehydrogenase complex in traumatic brain injury and measurement of pyruvate dehydrogenase enzyme by dipstick test. J. Emerg.Trauma Shock 2, 67-72. doi: 10.4103/0974-2700.50739
102. Shen, J. (2013). Modeling the glutamate-glutamine neurotransmitter cycle. Front. Neuroenergetics 5:1. doi: 10.3389/fnene.2013.00001
103. Signoretti, S., Vagnozzi, R., Tavazzi, B., and Lazzarino, G. (2010). Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications. Neurosurg. Focus 29, E1. doi: 10.3171/2010.9.FOCUS10183
104. Singh, I. N., Gilmer, L. K., Miller, D. M., Cebak, J. E., Wang, J. A., and Hall, E. D. (2013). Phenelzine mitochondrial functional preservation and neuroprotection after traumatic brain injury related to scavenging of the lipid peroxidation-derived aldehyde 4-hydroxy-2-nonenal. J. Cereb. Blood Flow Metab. 33, 593-599. doi: 10.1038/jcbfm.2012.211
105. Starkov, A. A., Fiskum, G., Chinopoulos, C., Lorenzo, B. J., Browne, S. E., Patel, M. S., et al. (2004). Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J. Neurosci. 24, 7779-7788. doi: 10.1523/JNEUROSCI.1899-04.2004
106. Sutton, R. L., Hovda, D. A., Adelson, P. D., Benzel, E. C., and Becker, D. P. (1994). Metabolic changes following cortical contusion: relationships to edema and morphological changes. Acta Neurochir. Suppl.(Wien.) 60, 446-448.
107. Takahashi, S., Izawa, Y., and Suzuki, N. (2012). Astroglial pentose phosphate pathway rates in response to high-glucose environments. ASN Neuro. 4, 71-88. doi: 10.1042/AN20120002
108. Tyurin, V. A., Tyurina, Y. Y., Borisenko, G. G., Sokolova, T. V., Ritov, V. B., Quinn, P. J., et al. (2000). Oxidative stress following traumatic brain injury in rats: quantitation of biomarkers and detection of free radical intermediates. J. Neurochem. 75, 2178-2189. doi: 10.1046/j.1471-4159.2000.0752178.x
109. Vagnozzi, R., Marmarou, A., Tavazzi, B., Signoretti, S., Di Pierro, D., del Bolgia, F., et al. (1999). Changes of cerebral energy metabolism and lipid peroxidation in rats leading to mitochondrial dysfunction after diffuse brain injury. J. Neurotrauma 16, 903-913. doi: 10.1089/neu.1999.16.903
110. Van den Berg, C. J., Krzalic, L. J., Mela, P., and Waelsch, H. (1969). Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain. Biochem. J. 113, 281-290.
111. van Landeghem, F. K. H., Weiss, T., Oehmichen, M., and von Deimling, A. (2006). Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury. J. Neurotrauma 23, 1518-1528. doi: 10.1089/neu.2006.23.1518
112. Verweij, B. H., Muizelaar, J. P., Vinas, F. C., Peterson, P. L., Xiong, Y., and Lee, C. P. (2000). Impaired cerebral mitochondrial function after traumatic brain injury in humans. J. Neurosurg. 93, 815-820. doi: 10.3171/jns.2000.93.5.0815
113. Vespa, P. M., McArthur, D., O'Phelan, K., Glenn, T., Etchepare, M., Kelly, D., et al. (2003). 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. 23, 865-877. doi: 10.1097/01.WCB.0000076701.45782.EF
114. Vespa, P. M., Miller, C., McArthur, D., Eliseo, M., Etchepare, M., Hirt, D., et al. (2007). Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Crit. Care Med. 35, 2830-2836. doi: 10.1097/01.CCM.0000295667.66853.BC
115. Waniewski, R. A., and Martin, D. L. (1998). Preferential utilization of acetate by astrocytes is attributable to transport. J. Neurosci. 18, 5225-5233.
116. Xing, G., Ren, M., O'Neill, J. T., Sharma, P., Verma, A., and Watson, W. D. (2012). Pyruvate dehydrogenase phosphatase1 mRNA expression is divergently and dynamically regulated between rat cerebral cortex, hippocampus and thalamus after traumatic brain injury: a potential biomarker of TBI-induced hyper- and hypo-glycaemia and neuronal vulnerability. Neurosci. Lett. 525, 140-145. doi: 10.1016/j.neulet.2012.07.055
117. Xing, G., Ren, M., Watson, W. A., O'Neil, J. T., and Verma, A. (2009). Traumatic brain injury-induced expression and phosphorylation of pyruvate dehydrogenase: a mechanism of dysregulated glucose metabolism. Neurosci. Lett. 454, 38-42. doi: 10.1016/j.neulet.2009.01.047
118. Xiong, Y., Gu, Q., Peterson, P. L., Muizelaar, J. P., and Lee, C. P. (1997). Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J. Neurotrauma 14, 23-34. doi: 10.1089/neu.1997.14.23
119. Xiong, Y., Peterson, P. L., Verweij, B. H., Vinas, F. C., Muizelaar, J. P., and Lee, C. P. (1998). Mitochondrial dysfunction after experimental traumatic brain injury: combined efficacy of SNX-111 and U-101033E. J. Neurotrauma 15, 531-544. doi: 10.1089/neu.1998.15.531
120. Yamaki, T., Yoshino, E., Fujimoto, M., Ohmori, Y., Imahori, Y., and Ueda, S. (1996). Chronological positron emission tomographic study of severe diffuse brain injury in the chronic stage. J. Trauma 40, 50-56. doi: 10.1097/00005373-199601000-00010
121. Yi, J. H., and Hazell, A. S. (2006). Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem. Int. 48, 394-403. doi: 10.1016/j.neuint.2005.12.001
122. Yoshino, A., Hovda, D. A., Kawamata, T., Katayama, Y., and Becker, D. P. (1991). Dynamic changes in local cerebral glucose utilization following cerebral concussion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res. 561, 106-119. doi: 10.1016/0006-8993(91)90755-K
123. Yu, A. C., Drejer, J., Hertz, L., and Schousboe, A. (1983). Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J. Neurochem. 41, 1484-1487. doi: 10.1111/j.1471-4159.1983.tb00849.x
124. Zamzami, N., Hirsch, T., Dallaporta, B., Petit, P. X., and Kroemer, G. (1997). Mitochondrial implication in accidental and programmed cell death: apoptosis and necrosis. J. Bioenerg. Biomembr. 29, 185-193. doi: 10.1023/A:1022694131572
125. Zanier, E. R., Lee, S. M., Vespa, P. M., Giza, C. C., and Hovda, D. A. (2003). Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury. J. Neurotrauma 20, 409-420. doi: 10.1089/089771503765355496