Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury

Journal of Bioenergetics and Biomembranes

Volumn 47, Issue 1-2, 2015, Pages 133-148

  Gajavelli, Shyam ^a   Sinha, Vishal K ^a   Mazzeo, Anna T ^c   Spurlock, Markus S ^a   Lee, Stephanie W ^a   Ahmed, Aminul I ^a   Yokobori, Shoji ^b   Bullock, Ross M ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b NIPPON MEDICAL SCHOOL   (Japan)

^c UNIVERSITY OF TURIN   (Italy)

Author keywords

Cyclosporine A; Hypoxia; KTP; Mitochondrial dynamics; Mitochondrial dysfunction; Penetrating traumatic brain injury; Secondary brain injury

Indexed keywords

CYCLOSPORIN A; OXYGEN; PLACEBO; CARRIER PROTEIN; MITOCHONDRIAL PERMEABILITY TRANSITION PORE;

BIOGENESIS; BRAIN METABOLISM; CENTRAL NERVOUS SYSTEM; CRITICAL ILLNESS; DISEASE SEVERITY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; GLIA; HUMAN; METABOLIC CAPACITY; MITOCHONDRIAL DYNAMICS; MITOCHONDRION; NERVE CELL; NEUROPROTECTION; NONHUMAN; PATHOPHYSIOLOGY; REVIEW; TRAUMATIC BRAIN INJURY; ADULT; ANIMAL; ASTROCYTE; BRAIN INJURIES; METABOLISM; NEURODEGENERATIVE DISEASES; PATHOLOGY;

ADULT; ANIMALS; ASTROCYTES; BRAIN INJURIES; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; NEURODEGENERATIVE DISEASES; NEURONS;

EID: 84922483772     PISSN: 0145479X     EISSN: 15736881     Source Type: Journal    
DOI: 10.1007/s10863-014-9589-1     Document Type: Review

References (159)

1. Adamczak SE, de Rivero Vaccari JP, Dale G, Brand FJ 3rd, Nonner D, Bullock MR et al (2014) Pyroptotic neuronal cell death mediated by the AIM2 inflammasome. J Cereb Blood Flow Metab 34(4):621–629. doi:10.1038/jcbfm.2013.236
2. Alessandri B, Rice AC, Levasseur J, DeFord M, Hamm RJ, Bullock MR (2002) Cyclosporin a improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats. J Neurotrauma 19(7):829–841. doi:10.1089/08977150260190429
3. Alessandri BGM, Levasseur JE, Bullock M (2009) Lactate and glucose as energy substrates and their role in traumatic brain injury and therapy. [Review]. Future Neurol 4(2):209–228. doi:10.2217/14796708.4.2.209
4. Aminmansour B, Fard SA, Habibabadi MR, Moein P, Norouzi R, Naderan M (2014) The efficacy of cyclosporine-a on diffuse axonal injury after traumatic brain injury. Adv Biomed Res 3:35. doi:10.4103/2277-9175.125031
5. Amo T, Sato S, Saiki S, Wolf AM, Toyomizu M, Gautier CA et al (2011) Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects. Neurobiol Dis 41(1):111–118. doi:10.1016/j.nbd.2010.08.027
6. Arun P, Ariyannur PS, Moffett JR, Xing G, Hamilton K, Grunberg NE et al (2010) Metabolic acetate therapy for the treatment of traumatic brain injury. J Neurotrauma 27(1):293–298. doi:10.1089/neu.2009.0994
7. Balan IS, Saladino AJ, Aarabi B, Castellani RJ, Wade C, Stein DM et al (2013) Cellular alterations in human traumatic brain injury: changes in mitochondrial morphology reflect regional levels of injury severity. J Neurotrauma 30(5):367–381. doi:10.1089/neu.2012.2339
8. Barrientos A, Fontanesi F, Diaz F (2009) Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using polarography and spectrophotometric enzyme assays. Curr Protoc Hum Genet, Chapter 19, Unit19 13, doi:10.1002/0471142905.hg1903s63
9. Baskaya MK, Dogan A, Temiz C, Dempsey RJ (2000) Application of 2,3,5-triphenyltetrazolium chloride staining to evaluate injury volume after controlled cortical impact brain injury: role of brain edema in evolution of injury volume. J Neurotrauma 17(1):93–99
10. Bhatt DP, Houdek HM, Watt JA, Rosenberger TA (2013) Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis. Neurochem Int 62(3):296–305. doi:10.1016/j.neuint.2013.01.004
11. Binder S, Corrigan JD, Langlois JA (2005) The public health approach to traumatic brain injury: an overview of CDC’s research and programs. J Head Trauma Rehabil 20(3):189–195
12. Blaya MO, Bramlett HM, Naidoo J, Pieper AA, Dietrich WD (2014) Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury. J Neurotrauma 31(5):476–486. doi:10.1089/neu.2013.3135
13. Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG et al (2006) Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 60(2):223–235. doi:10.1002/ana.20899
14. Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F et al (2014) Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med 40(3):412–421. doi:10.1007/s00134-013-3203-6
15. Brealey D, Karyampudi S, Jacques TS, Novelli M, Stidwill R, Taylor V et al (2004) Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure. Am J Physiol Regul Integr Comp Physiol 286(3):R491–R497. doi:10.1152/ajpregu.00432.2003
16. Brophy GM, Mazzeo AT, Brar S, Alves OL, Bunnell K, Gilman C et al (2013) Exposure of cyclosporin a in whole blood, cerebral spinal fluid, and brain extracellular fluid dialysate in adults with traumatic brain injury. J Neurotrauma 30(17):1484–1489. doi:10.1089/neu.2012.2524
17. Bullock R, Maxwell WL, Graham DI, Teasdale GM, Adams JH (1991) Glial swelling following human cerebral contusion: an ultrastructural study. J Neurol Neurosurg Psychiatry 54(5):427–434
18. Carpenter KL, Jalloh I, Gallagher CN, Grice P, Howe DJ, Mason A et al (2014) (13)C-labelled microdialysis studies of cerebral metabolism in TBI patients. Eur J Pharm Sci 57:87–97. doi:10.1016/j.ejps.2013.12.012
19. Carre JE, Singer M (2008) Cellular energetic metabolism in sepsis: the need for a systems approach. Biochim Biophys Acta 1777(7–8):763–771. doi:10.1016/j.bbabio.2008.04.024
20. Carre JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M et al (2010) Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med 182(6):745–751. doi:10.1164/rccm.201003-0326OC
21. Cartagena CM, Phillips KL, Tortella FC, Dave JR, Schmid KE (2014) Temporal alterations in aquaporin and transcription factor HIF1alpha expression following penetrating ballistic-like brain injury (PBBI). Mol Cell Neurosci 60:81–87. doi:10.1016/j.mcn.2014.04.005
22. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL et al (2011) Broad activation of the ubiquitin-proteasome system by parkin is critical for mitophagy. Hum Mol Genet 20(9):1726–1737. doi:10.1093/hmg/ddr048
23. Chen T, Qian YZ, Di X, Rice A, Zhu JP, Bullock R (2000) Lactate/glucose dynamics after rat fluid percussion brain injury. J Neurotrauma 17(2):135–142
24. Cherian L, Goodman JC, Robertson CS (1997) Hyperglycemia increases brain injury caused by secondary ischemia after cortical impact injury in rats. Crit Care Med 25(8):1378–1383
25. Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, Chin LS et al (2004) Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson’s and Alzheimer’s diseases. J Biol Chem 279(13):13256–13264. doi:10.1074/jbc.M314124200
26. Clark JF, Doepke A, Filosa JA, Wardle RL, Lu A, Meeker TJ et al (2006) N-acetylaspartate as a reservoir for glutamate. Med Hypotheses 67(3):506–512. doi:10.1016/j.mehy.2006.02.047
27. Clausen T, Bullock R (2001) Medical treatment and neuroprotection in traumatic brain injury. Curr Pharm Des 7(15):1517–1532
28. Clifton GL, Valadka A, Zygun D, Coffey CS, Drever P, Fourwinds S et al (2011) Very early hypothermia induction in patients with severe brain injury (the national acute brain injury study: hypothermia II): a randomised trial. Lancet Neurol 10(2):131–139. doi:10.1016/S1474-4422(10)70300-8
29. Conley YP, Okonkwo DO, Deslouches S, Alexander S, Puccio AM, Beers SR et al (2014) Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury. J Neurotrauma 31(1):34–41. doi:10.1089/neu.2013.2855
30. Coulombe J, Gamage P, Gray MT, Zhang M, Tang MY, Woulfe J et al (2014) Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system. Front Aging Neurosci 6:129. doi:10.3389/fnagi.2014.00129
31. Dare AJ, Phillips AR, Hickey AJ, Mittal A, Loveday B, Thompson N et al (2009) A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome. Free Radic Biol Med 47(11):1517–1525. doi:10.1016/j.freeradbiomed.2009.08.019
32. Daugherty WP, Levasseur JE, Sun D, Spiess BD, Bullock MR (2004) Perfluorocarbon emulsion improves cerebral oxygenation and mitochondrial function after fluid percussion brain injury in rats. Neurosurgery 54(5):1223–1230, discussion 1230
33. Davis CH, Kim KY, Bushong EA, Mills EA, Boassa D, Shih T et al (2014) Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci U S A 111(26):9633–9638. doi:10.1073/pnas.1404651111
34. De Fazio M, Rammo R, O’Phelan K, Bullock MR (2011) Alterations in cerebral oxidative metabolism following traumatic brain injury. Neurocrit Care 14(1):91–96. doi:10.1007/s12028-010-9494-3
35. De Vos KJ, Grierson AJ, Ackerley S, Miller CC (2008) Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 31:151–173. doi:10.1146/annurev.neuro.31.061307.090711
36. DeBerardinis RJ, Thompson CB (2012) Cellular metabolism and disease: what do metabolic outliers teach us? Cell 148(6):1132–1144. doi:10.1016/j.cell.2012.02.032
37. Duncan JE, Goldstein LS (2006) The genetics of axonal transport and axonal transport disorders. PLoS Genet 2(9):e124. doi:10.1371/journal.pgen.0020124
38. Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D et al (2009) Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol 187(7):1023–1036. doi:10.1083/jcb.200906084
39. Faithfull NS (1992) Oxygen delivery from fluorocarbon emulsions–aspects of convective and diffusive transport. Biomater Artif Cells Immobilization Biotechnol 20(2–4):797–804
40. Fu ES, Tummala RP (2005) Neuroprotection in brain and spinal cord trauma. Curr Opin Anaesthesiol 18(2):181–187. doi:10.1097/01.aco.0000162838.56344.88
41. Gaetz M (2004) The neurophysiology of brain injury. Clin Neurophysiol 115(1):4–18
42. Gajavelli Shyam AB, Spurlock M, Diaz D, Burks S, Bomberger C, Bidot CJ, Yokobori S, Diaz J, Sanchez-Chavez J, Bullock R (Ed.) (2012) Immunohistochemical correlation of novel biomarkers with neurodegeneration in rat models of brain injury (Applications of Immunocytochemistry)
43. Galley HF (2011) Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth 107(1):57–64. doi:10.1093/bja/aer093
44. Gantner D, Moore EM, Cooper DJ (2014) Intravenous fluids in traumatic brain injury: what’s the solution? Curr Opin Crit Care 20(4):385–389. doi:10.1097/MCC.0000000000000114
45. Gilmer LK, Roberts KN, Joy K, Sullivan PG, Scheff SW (2009) Early mitochondrial dysfunction after cortical contusion injury. J Neurotrauma 26(8):1271–1280. doi:10.1089/neu.2008.0857
46. Gilmer LK, Ansari MA, Roberts KN, Scheff SW (2010) Age-related mitochondrial changes after traumatic brain injury. J Neurotrauma 27(5):939–950. doi:10.1089/neu.2009.1181
47. Gomez LA, Monette JS, Chavez JD, Maier CS, Hagen TM (2009) Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart. Arch Biochem Biophys 490(1):30–35. doi:10.1016/j.abb.2009.08.002
48. Gordon GR, Choi HB, Rungta RL, Ellis-Davies GC, MacVicar BA (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456(7223):745–749. doi:10.1038/nature07525
49. Gurevich B, Talmor D, Artru AA, Katcko L, Geva D, Gurman G et al (1997) Brain edema, hemorrhagic necrosis volume, and neurological status with rapid infusion of 0.45 % saline or 5 % dextrose in 0.9 % saline after closed head trauma in rats. Anesth Analg 84(3):554–559
50. Halestrap AP (2013) The SLC16 gene family - structure, role and regulation in health and disease. Mol Aspects Med 34(2–3):337–349. doi:10.1016/j.mam.2012.05.003
51. Hanafy KA, Selim MH (2012) Antioxidant strategies in neurocritical care. Neurotherapeutics 9(1):44–55. doi:10.1007/s13311-011-0085-6
52. Harbauer AB, Zahedi RP, Sickmann A, Pfanner N, Meisinger C (2014) The protein import machinery of mitochondria-a regulatory hub in metabolism, stress, and disease. Cell Metab 19(3):357–372. doi:10.1016/j.cmet.2014.01.010
53. Hatton J, Rosbolt B, Empey P, Kryscio R, Young B (2008) Dosing and safety of cyclosporine in patients with severe brain injury. J Neurosurg 109(4):699–707. doi:10.3171/jns/2008/109/10/0699
54. Haut ER, Kalish BT, Cotton BA, Efron DT, Haider AH, Stevens KA et al (2011) Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: a national trauma data bank analysis. Ann Surg 253(2):371–377. doi:10.1097/SLA.0b013e318207c24f
55. Henry B, Emilie C, Bertrand P, Erwan D (2012) Cerebral microdialysis and PtiO2 to decide unilateral decompressive craniectomy after brain gunshot. J Emerg Trauma Shock 5(1):103–105. doi:10.4103/0974-2700.93101
56. Hertz L (2006) Glutamate, a neurotransmitter–and so much more. A synopsis of Wierzba III. Neurochem Int 48(6–7):416–425. doi:10.1016/j.neuint.2005.12.021
57. Hertz NT, Berthet A, Sos ML, Thorn KS, Burlingame AL, Nakamura K et al (2013) A neo-substrate that amplifies catalytic activity of parkinson’s-disease-related kinase PINK1. Cell 154(4):737–747. doi:10.1016/j.cell.2013.07.030
58. Hoane MR, Swan AA, Heck SE (2011) The effects of a high-fat sucrose diet on functional outcome following cortical contusion injury in the rat. Behav Brain Res 223(1):119–124. doi:10.1016/j.bbr.2011.04.028
59. Hughes SD, Kanabus M, Anderson G, Hargreaves IP, Rutherford T, O’Donnell M et al (2014) The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells. J Neurochem 129(3):426–433. doi:10.1111/jnc.12646
60. Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C et al (2009) Sodium lactate versus mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med 35(3):471–479. doi:10.1007/s00134-008-1283-5
61. Investigators, S. S., Australian, New Zealand Intensive Care Society Clinical Trials, G., Australian Red Cross Blood, S., George Institute for International, H, Myburgh J et al (2007) Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 357(9):874–884. doi:10.1056/NEJMoa067514
62. Ji J, Tyurina YY, Tang M, Feng W, Stolz DB, Clark RS et al (2012) Mitochondrial injury after mechanical stretch of cortical neurons in vitro: biomarkers of apoptosis and selective peroxidation of anionic phospholipids. J Neurotrauma 29(5):776–788. doi:10.1089/neu.2010.1602
63. Jin SM, Youle RJ (2012) PINK1- and parkin-mediated mitophagy at a glance. J Cell Sci 125(Pt 4):795–799. doi:10.1242/jcs.093849
64. Kilbaugh TJ, Bhandare S, Lorom DH, Saraswati M, Robertson CL, Margulies SS (2011) Cyclosporin a preserves mitochondrial function after traumatic brain injury in the immature rat and piglet. J Neurotrauma 28(5):763–774. doi:10.1089/neu.2010.1635
65. Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462(2):245–253. doi:10.1016/j.abb.2007.03.034
66. Kirkinezos IG, Moraes CT (2001) Reactive oxygen species and mitochondrial diseases. Semin Cell Dev Biol 12(6):449–457. doi:10.1006/scdb.2001.0282
67. Koizumi J, Shiraishi H (1970) Fine structural changes of mitochondria in cerebral edema and dehydration. Arch Histol Jpn 32(3):241–249
68. Kollmann TR, Levy O, Montgomery RR, Goriely S (2012) Innate immune function by toll-like receptors: distinct responses in newborns and the elderly. Immunity 37(5):771–783. doi:10.1016/j.immuni.2012.10.014
69. Korde AS, Sullivan PG, Maragos WF (2005) The uncoupling agent 2,4-dinitrophenol improves mitochondrial homeostasis following Striatal quinolinic acid injections. J Neurotrauma 22(10):1142–1149. doi:10.1089/neu.2005.22.1142
70. Kortbeek JB, Al Turki SA, Ali J, Antoine JA, Bouillon B, Brasel K et al (2008) Advanced trauma life support, 8th edition, the evidence for change. J Trauma 64(6):1638–1650. doi:10.1097/TA.0b013e3181744b03
71. Kozlov AV, Bahrami S, Calzia E, Dungel P, Gille L, Kuznetsov AV et al (2011) Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure? Ann Intensive Care 1(1):41. doi:10.1186/2110-5820-1-41
72. Kristal BS, Stavrovskaya IG, Narayanan MV, Krasnikov BF, Brown AM, Beal MF et al (2004) The mitochondrial permeability transition as a target for neuroprotection. J Bioenerg Biomembr 36(4):309–312. doi:10.1023/b:jobb.0000041759.35731.70
73. Kwon TH, Sun D, Daugherty WP, Spiess BD, Bullock MR (2005) Effect of perfluorocarbons on brain oxygenation and ischemic damage in an acute subdural hematoma model in rats. J Neurosurg 103(4):724–730. doi:10.3171/jns.2005.103.4.0724
74. Langlois JA, Marr A, Mitchko J, Johnson RL (2005) Tracking the silent epidemic and educating the public: CDC’s traumatic brain injury-associated activities under the TBI Act of 1996 and the Children’s health Act of 2000. J Head Trauma Rehabil 20(3):196–204
75. Lanza IR, Nair KS (2010) Mitochondrial metabolic function assessed in vivo and in vitro. Curr Opin Clin Nutr Metab Care 13(5):511–517. doi:10.1097/MCO.0b013e32833cc93d
76. Lifshitz J, Sullivan PG, Hovda DA, Wieloch T, McIntosh TK (2004) Mitochondrial damage and dysfunction in traumatic brain injury. Mitochondrion 4(5–6):705–713. doi:10.1016/j.mito.2004.07.021
77. Liu X, Weaver D, Shirihai O, Hajnoczky G (2009) Mitochondrial ‘kiss-and-run’: interplay between mitochondrial motility and fusion-fission dynamics. EMBO J 28(20):3074–3089. doi:10.1038/emboj.2009.255
78. Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P et al (2012) Parkinson’s disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet 8(3):e1002537. doi:10.1371/journal.pgen.1002537
79. Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA et al (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189(2):211–221. doi:10.1083/jcb.200910140
80. Mazzeo AT, Kunene NK, Gilman CB, Hamm RJ, Hafez N, Bullock MR (2006) Severe human traumatic brain injury, but not cyclosporin a treatment, depresses activated T lymphocytes early after injury. J Neurotrauma 23(6):962–975. doi:10.1089/neu.2006.23.962
81. Mazzeo AT, Alves OL, Gilman CB, Hayes RL, Tolias C, Niki Kunene K et al (2008) Brain metabolic and hemodynamic effects of cyclosporin A after human severe traumatic brain injury: a microdialysis study. Acta Neurochir (Wien) 150(10):1019–1031. doi:10.1007/s00701-008-0021-7, discussion 1031
82. Mazzeo AT, Beat A, Singh A, Bullock MR (2009a) The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI. Exp Neurol 218(2):363–370. doi:10.1016/j.expneurol.2009.05.026
83. Mazzeo AT, Brophy GM, Gilman CB, Alves OL, Robles JR, Hayes RL et al (2009b) Safety and tolerability of cyclosporin a in severe traumatic brain injury patients: results from a prospective randomized trial. J Neurotrauma 26(12):2195–2206. doi:10.1089/neu.2009.1012
84. Miller DM, Singh IN, Wang JA, Hall ED (2013) Administration of the Nrf2-ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo. Free Radic Biol Med 57:1–9. doi:10.1016/j.freeradbiomed.2012.12.011
85. Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30(12):4232–4240. doi:10.1523/JNEUROSCI. 6248-09.2010
86. Moraes CT (2014) A magic bullet to specifically eliminate mutated mitochondrial genomes from patients’ cells. EMBO Mol Med 6(4):434–435. doi:10.1002/emmm.201303769
87. Morawetz RB, DeGirolami U, Ojemann RG, Marcoux FW, Crowell RM (1978) Cerebral blood flow determined by hydrogen clearance during middle cerebral artery occlusion in unanesthetized monkeys. Stroke 9(2):143–149
88. Moro N, Sutton RL (2010) Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat. Exp Neurol 225(2):391–401. doi:10.1016/j.expneurol.2010.07.013
89. Moro N, Ghavim SS, Hovda DA, Sutton RL (2011) Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury. Neurosci Lett 491(2):158–162. doi:10.1016/j.neulet.2011.01.029
90. Moro N, Ghavim S, Harris NG, Hovda DA, Sutton RL (2013) Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury. Brain Res 1535:124–136. doi:10.1016/j.brainres.2013.08.044
91. Murakami Y, Wei G, Yang X, Lu XC, Leung LY, Shear DA et al (2012) Brain oxygen tension monitoring following penetrating ballistic-like brain injury in rats. [Research Support, U.S. Gov’t, Non-P.H.S.]. J Neurosci Methods 203(1):115–121. doi:10.1016/j.jneumeth.2011.09.025
92. Myburgh JA, Finfer S (2009) Albumin is a blood product too - is it safe for all patients? Crit Care Resusc 11(1):67–70
93. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB et al (2002) Clinical trials in head injury. J Neurotrauma 19(5):503–557. doi:10.1089/089771502753754037
94. Nguyen JV, Soto I, Kim KY, Bushong EA, Oglesby E, Valiente-Soriano FJ et al (2011) Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma. Proc Natl Acad Sci U S A 108(3):1176–1181. doi:10.1073/pnas.1013965108
95. Nordstrom CH, Nielsen TH (2014) Exogenous lactate supplementation to the injured brain: misleading conclusions with clinical implications. Intensive Care Med 40(6):919. doi:10.1007/s00134-014-3297-5
96. Nordstrom CH, Nielsen TH, Jacobsen A (2013) Techniques and strategies in neurocritical care originating from southern Scandinavia. J Rehabil Med 45(8):710–717. doi:10.2340/16501977-1157
97. Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148(6):1145–1159. doi:10.1016/j.cell.2012.02.035
98. Oehmichen M, Walter T, Meissner C, Friedrich HJ (2003) Time course of cortical hemorrhages after closed traumatic brain injury: statistical analysis of posttraumatic histomorphological alterations. J Neurotrauma 20(1):87–103. doi:10.1089/08977150360517218
99. Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T et al (2012) Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485(7397):251–255. doi:10.1038/nature10992
100. Okonkwo DO, Buki A, Siman R, Povlishock JT (1999) Cyclosporin a limits calcium-induced axonal damage following traumatic brain injury. Neuroreport 10(2):353–358
101. Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277(34):30409–30412. doi:10.1074/jbc.R200006200
102. Palikaras K, Tavernarakis N (2014) Mitochondrial homeostasis: the interplay between mitophagy and mitochondrial biogenesis. Exp Gerontol 56:182–188. doi:10.1016/j.exger.2014.01.021
103. Palmer CS, Osellame LD, Stojanovski D, Ryan MT (2011) The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Cell Signal 23(10):1534–1545. doi:10.1016/j.cellsig.2011.05.021
104. Pandya JD, Nukala VN, Sullivan PG (2013) Concentration dependent effect of calcium on brain mitochondrial bioenergetics and oxidative stress parameters. Front Neuroenergetics 5:10. doi:10.3389/fnene.2013.00010
105. Parra V, Verdejo HE, Iglewski M, Del Campo A, Troncoso R, Jones D et al (2014) Insulin stimulates mitochondrial fusion and function in cardiomyocytes via the Akt-mTOR-NFkappaB-Opa-1 signaling pathway. Diabetes 63(1):75–88. doi:10.2337/db13-0340
106. Perez-Pinzon MA, Stetler RA, Fiskum G (2012) Novel mitochondrial targets for neuroprotection. J Cereb Blood Flow Metab 32(7):1362–1376. doi:10.1038/jcbfm.2012.32
107. Perri BR, Smith DH, Murai H, Sinson G, Saatman KE, Raghupathi R et al (1997) Metabolic quantification of lesion volume following experimental traumatic brain injury in the rat. J Neurotrauma 14(1):15–22
108. Piantadosi CA, Suliman HB (2012) Redox regulation of mitochondrial biogenesis. Free Radic Biol Med 53(11):2043–2053. doi:10.1016/j.freeradbiomed.2012.09.014
109. Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N et al (2008) Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359(5):473–481. doi:10.1056/NEJMoa071142
110. Prins M, Matsumoto J (2014) The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury. J Lipid Res. doi:10.1194/jlr.R046706
111. Prins M, Greco T, Alexander D, Giza CC (2013) The pathophysiology of traumatic brain injury at a glance. Dis Model Mech 6(6):1307–1315. doi:10.1242/dmm.011585
112. Procaccio V, Bris C, Chao de la Barca JM, Oca F, Chevrollier A, Amati-Bonneau P et al (2014) Perspectives of drug-based neuroprotection targeting mitochondria. Rev Neurol (Paris) 170(5):390–400. doi:10.1016/j.neurol.2014.03.005
113. Ren C, Zoltewicz S, Guingab-Cagmat J, Anagli J, Gao M, Hafeez A et al (2013) Different expression of ubiquitin C-terminal hydrolase-L1 and alphaII-spectrin in ischemic and hemorrhagic stroke: potential biomarkers in diagnosis. Brain Res 1540:84–91. doi:10.1016/j.brainres.2013.09.051
114. Rho JM, Sankar R (2008) The ketogenic diet in a pill: is this possible? Epilepsia 49(Suppl 8):127–133. doi:10.1111/j.1528-1167.2008.01857.x
115. Rockswold SB, Rockswold GL, Zaun DA, Liu J (2013) A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg 118(6):1317–1328. doi:10.3171/2013.2.JNS121468
116. Russo GJ, Louie K, Wellington A, Macleod GT, Hu F, Panchumarthi S et al (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci 29(17):5443–5455. doi:10.1523/JNEUROSCI. 5417-08.2009
117. Sauerbeck A, Gao J, Readnower R, Liu M, Pauly JR, Bing G et al (2011) Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. Exp Neurol 227(1):128–135. doi:10.1016/j.expneurol.2010.10.003
118. Schell JC, Rutter J (2013) The long and winding road to the mitochondrial pyruvate carrier. Cancer Metab 1(1):6. doi:10.1186/2049-3002-1-6
119. Segel R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D et al (2011) A safety trial of high dose glyceryl triacetate for Canavan disease. Mol Genet Metab 103(3):203–206. doi:10.1016/j.ymgme.2011.03.012
120. Signoretti S, Marmarou A, Tavazzi B, Dunbar J, Amorini AM, Lazzarino G et al (2004) The protective effect of cyclosporin a upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury. J Neurotrauma 21(9):1154–1167. doi:10.1089/neu.2004.21.1154
121. Signoretti S, Marmarou A, Aygok GA, Fatouros PP, Portella G, Bullock RM (2008) Assessment of mitochondrial impairment in traumatic brain injury using high-resolution proton magnetic resonance spectroscopy. J Neurosurg 108(1):42–52. doi:10.3171/jns/2008/108/01/0042
122. Simmons ML, Frondoza CG, Coyle JT (1991) Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45(1):37–45
123. Singer M (2007) Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit Care Med 35(9 Suppl):S441–S448. doi:10.1097/01.CCM.0000278049.48333.78
124. Singh IN, Sullivan PG, Deng Y, Mbye LH, Hall ED (2006) Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J Cereb Blood Flow Metab 26(11):1407–1418. doi:10.1038/sj.jcbfm.9600297
125. Soane L, Kahraman S, Kristian T, Fiskum G (2007) Mechanisms of impaired mitochondrial energy metabolism in acute and chronic neurodegenerative disorders. J Neurosci Res 85(15):3407–3415. doi:10.1002/jnr.21498
126. Soustiel JF, Larisch S (2010) Mitochondrial damage: a target for new therapeutic horizons. Neurotherapeutics 7(1):13–21. doi:10.1016/j.nurt.2009.11.001
127. Soustiel JF, Sviri GE (2007) Monitoring of cerebral metabolism: non-ischemic impairment of oxidative metabolism following severe traumatic brain injury. Neurol Res 29(7):654–660. doi:10.1179/016164107x240017
128. Suliman HB, Piantadosi CA (2014) Mitochondrial Biogenesis: Regulation By Endogenous Gases during Inflammation and Organ Stress. Curr Pharm Des
129. Sullivan PG, Thompson MB, Scheff SW (1999) Cyclosporin a attenuates acute mitochondrial dysfunction following traumatic brain injury. Exp Neurol 160(1):226–234. doi:10.1006/exnr.1999.7197
130. Sullivan PG, Thompson M, Scheff SW (2000) Continuous infusion of cyclosporin a postinjury significantly ameliorates cortical damage following traumatic brain injury. Exp Neurol 161(2):631–637. doi:10.1006/exnr.1999.7282
131. Traeger EC, Rapin I (1998) The clinical course of Canavan disease. Pediatr Neurol 18(3):207–212
132. Tsukada H, Ohba H, Nishiyama S, Kanazawa M, Kakiuchi T, Harada N (2014) PET imaging of ischemia-induced impairment of mitochondrial complex I function in monkey brain. J Cereb Blood Flow Metab 34(4):708–714. doi:10.1038/jcbfm.2014.5
133. Twig G, Hyde B, Shirihai OS (2008) Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 1777(9):1092–1097. doi:10.1016/j.bbabio.2008.05.001
134. Uchino H, Elmer E, Uchino K, Lindvall O, Siesjo BK (1995) Cyclosporin a dramatically ameliorates CA1 hippocampal damage following transient forebrain ischaemia in the rat. Acta Physiol Scand 155(4):469–471
135. Valadka AB, Gopinath SP, Contant CF, Uzura M, Robertson CS (1998) Relationship of brain tissue PO2 to outcome after severe head injury. Crit Care Med 26(9):1576–1581
136. van den Brink WA, van Santbrink H, Avezaat CJ, Hogesteeger C, Jansen W, Kloos LM et al (1998) Monitoring brain oxygen tension in severe head injury: the Rotterdam experience. Acta Neurochir Suppl 71:190–194
137. Vaz R, Sarmento A, Borges N, Cruz C, Azevedo I (1997) Ultrastructural study of brain microvessels in patients with traumatic cerebral contusions. Acta Neurochir (Wien) 139(3):215–220
138. Verweij BH, Muizelaar JP, Vinas FC, Peterson PL, Xiong Y, Lee CP (2000) Impaired cerebral mitochondrial function after traumatic brain injury in humans. J Neurosurg 93(5):815–820. doi:10.3171/jns.2000.93.5.0815
139. Vespa PM, 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(7):865–877. doi:10.1097/01.WCB.0000076701.45782.EF
140. Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA et al (2005) Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab 25(6):763–774. doi:10.1038/sj.jcbfm.9600073
141. Vink R, Nimmo AJ (2009) Multifunctional drugs for head injury. Neurotherapeutics 6(1):28–42. doi:10.1016/j.nurt.2008.10.036
142. Vink R, Golding EM, Williams JP, McIntosh TK (1997) Blood glucose concentration does not affect outcome in brain trauma: A 31P MRS study. J Cereb Blood Flow Metab 17(1):50–53. doi:10.1097/00004647-199701000-00007
143. Waldmeier PC, Zimmermann K, Qian T, Tintelnot-Blomley M, Lemasters JJ (2003) Cyclophilin D as a drug target. Curr Med Chem 10(16):1485–1506
144. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283(5407):1482–1488
145. Wang N, Gray M, Lu XH, Cantle JP, Holley SM, Greiner E et al (2014) Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington’s disease. Nat Med 20(5):536–541. doi:10.1038/nm.3514
146. Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11(12):872–884. doi:10.1038/nrm3013
147. Williams AJ, Wei HH, Dave JR, Tortella FC (2007) Acute and delayed neuroinflammatory response following experimental penetrating ballistic brain injury in the rat. J Neuroinflammation 4:17. doi:10.1186/1742-2094-4-17
148. Xiong Y, Gu Q, Peterson PL, Muizelaar JP, Lee CP (1997) Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J Neurotrauma 14(1):23–34
149. Yao C, Williams AJ, Ottens AK, Lu XC, Liu MC, Hayes RL et al (2009) P43/pro-EMAPII: a potential biomarker for discriminating traumatic versus ischemic brain injury. J Neurotrauma 26(8):1295–1305. doi:10.1089/neu. 2008-0811
150. Yao C, Wei G, Lu XC, Yang W, Tortella FC, Dave JR (2011) Selective brain cooling in rats ameliorates intracerebral hemorrhage and edema caused by penetrating brain injury: possible involvement of heme oxygenase-1 expression. J Neurotrauma 28(7):1237–1245. doi:10.1089/neu.2010.1678
151. Yokobori S, Gajavelli S, Mondello S, Mo-Seaney J, Bramlett HM, Dietrich WD et al (2013a) Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model. J Neurosurg 118(2):370–380. doi:10.3171/2012.10.JNS12725
152. Yokobori S, Mazzeo AT, Gajavelli S, Bullock MR (2013) Mitochondrial Neuroprotection in Traumatic Brain Injury: Rationale and Therapeutic Strategies. CNS Neurol Disord Drug Targets
153. Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP (1991) Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res 561(1):106–119
154. Yun J, Finkel T (2014) Mitohormesis. Cell Metab 19(5):757–766. doi:10.1016/j.cmet.2014.01.011
155. Zamzami N, Kroemer G (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2(1):67–71. doi:10.1038/35048073
156. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W et al (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464(7285):104–107. doi:10.1038/nature08780
157. Zhang M, Li, W, Niu G, Leak RK, Chen J, Zhang F (2013) ATP induces mild hypothermia in rats but has a strikingly detrimental impact on focal cerebral ischemia. J Cereb Blood Flow Metab, 33(1), doi:10.1038/jcbfm.2012.146
158. Zhou Z, Sun D, Levasseur JE, Merenda A, Hamm RJ, Zhu J et al (2008) Perfluorocarbon emulsions improve cognitive recovery after lateral fluid percussion brain injury in rats. Neurosurgery 63(4):799–806. doi:10.1227/01.NEU.0000325493.51900.53, discussion 806–797
159. Zoltewicz JS, Mondello S, Yang B, Newsom KJ, Kobeissy F, Yao C et al (2013) Biomarkers track damage after graded injury severity in a rat model of penetrating brain injury. J Neurotrauma 30(13):1161–1169. doi:10.1089/neu.2012.2762