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Oxidative Stress and Free Radical Damage in Neurology pp 99–118Cite as

The Role of Reactive Oxygen Species in the Pathogenesis of Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) is a major cause of death in the young age group and leads to persisting neurological impairment in many of its victims. TBI involves a primary mechanical impact followed by the development of vasogenic and cytotoxic edema and impairment of energy metabolism and ionic homeostasis. Primary injury sets in motion a cascade of events that activate molecular and cellular responses. The relatively rapid process of primary cell death is followed by secondary degeneration of adjacent neurons having escaped the initial insult. The primary death of brain cells concomitantly also causes accumulation of harmful physiological substances such as glutamate, reactive oxygen species (ROS), and pro-inflammatory cytokines, creating a toxic environment for neighboring neurons and resulting in functional deficits. The mammalian brain is vulnerable to oxidative stress because of the high oxygen consumption needed for maintaining neuronal ion homoeostasis during the propagation of action potentials. Interruption of mitochondrial function involves oxidative stress and leads to impaired energy production, followed by rapidly developing brain damage. For nearly three decades, ROS have been the focus of interest as possible candidates for the elicitation of deleterious responses in the pathogenesis of ischemia and TBI; however, despite numerous clinical trials, no antioxidants have made their way into clinical practice. This chapter focuses on the role of oxidative stress and tissue antioxidant capacity in the pathogenesis of TBI. Oxidative stress in the brain and its biological targets are discussed along with the tissue’s intrinsic defense mechanisms, including antioxidant enzymes and low molecular weight antioxidants (LMWA). Post-TBI oxidative stress-induced damage is described, highlighting its major hallmarks, namely mitochondrial damage, lipid peroxidation, antioxidant enzymes, and LMWA. Finally, several therapeutic agents harboring antioxidant properties are presented at the end of the chapter for their implications in both experimental and clinical settings.

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References

  1. Evans PH. Free radicals in brain metabolism and pathology. Br Med Bull. 1993;49:577–87.

    CAS  PubMed  Google Scholar 

  2. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. Oxford: Oxford University Press; 1989. p. 160–5.

    Google Scholar 

  3. Marshall LF. Head injury: recent past, present, and future. Neurosurgery. 2000;47:546–61.

    Article  CAS  PubMed  Google Scholar 

  4. Bayir H, Clark RS, Kochanek PM. Promising strategies to minimize secondary brain injury after head trauma. Crit Care Med. 2003;31:S112–7.

    Article  CAS  PubMed  Google Scholar 

  5. Nolan S. Traumatic brain injury: a review. Crit Care Nurs Q. 2005;28:188–94.

    PubMed  Google Scholar 

  6. Nortje J, Menon DK. Traumatic brain injury: physiology, mechanisms, and outcome. Curr Opin Neurol. 2004;17:711–8.

    Article  PubMed  Google Scholar 

  7. Gentleman SM, Roberts GW, Gennarelli TA, Maxwell WL, Adams JH, Kerr S, Graham DI. Axonal injury: a universal consequence of fatal closed head injury? Acta Neuropathol. 1995;89:537–43.

    Article  CAS  PubMed  Google Scholar 

  8. Povlishock JT, Christman CW. The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J Neurotrauma. 1995;12:555–64.

    Article  CAS  PubMed  Google Scholar 

  9. Bramlett HM, Dietrich WD. Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res. 2007;161:125–41.

    Article  PubMed  Google Scholar 

  10. Yoles E, Schwartz M. Degeneration of spared axons following partial white matter lesion: implications for optic nerve neuropathies. Exp Neurol. 1988;153:1–7.

    Article  Google Scholar 

  11. Harrop JS, Sharan AD, Vaccaro AR, Przybylski GJ. The cause of neurologic deterioration after acute cervical spinal cord injury. Spine. 2001;26:340–6.

    Article  CAS  PubMed  Google Scholar 

  12. Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurgery. 1996;38:1176–95.

    Article  CAS  PubMed  Google Scholar 

  13. Shohami E, Beit-Yannai E, Horowitz M, Kohen R, Beit-Yannai E, Horowitz M, Kohen R. Oxidative stress in closed-head injury: brain antioxidant capacity as an indicator of functional outcome. J Cereb Blood Flow Metab. 1997;17:1007–19.

    Article  CAS  PubMed  Google Scholar 

  14. Shohami E, Ginis I, Hallenbeck JM. Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Factor Rev. 1999;10:119–30.

    Article  CAS  PubMed  Google Scholar 

  15. Beattie MS, Farooqui AA, Bresnahan JC. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma. 2000;17:915–25.

    Article  CAS  PubMed  Google Scholar 

  16. Schwartz M, Yoles E. Self-destructive and self-protective processes in the damaged optic nerve: implications for glaucoma [comment]. Invest Ophthalmol Vis Sci. 2000;41:349–51.

    CAS  PubMed  Google Scholar 

  17. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97:1634–58.

    Article  CAS  Google Scholar 

  18. Kohen R, Yamamoto Y, Cundy KC, Ames BN. Antioxidant activity of carnosine, homocarnosine and anserine present in muscle and brain. Proc Natl Acad Sci U S A. 1988;85:3175−9.

    Article  PubMed  Google Scholar 

  19. Kohen R, Nyska A. Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol. 2002;30:620–50.

    Article  CAS  PubMed  Google Scholar 

  20. Dugan LL, Choi DW. Excitotoxicity, free radicals and cell membrane changes. Ann Neurol. 1994;35:517−21.

    Article  Google Scholar 

  21. Gracy RW, Talent JM, Kong Y, Conrad CC. Reactive oxygen species: the unavoidable environmental insult? Mutat Res. 1999;428:17–22.

    CAS  PubMed  Google Scholar 

  22. Levine RL, Stadtman ER. Oxidative modification of proteins during aging. Exp Gerontol. 2001;36:1495–502.

    Article  CAS  PubMed  Google Scholar 

  23. Davis KJ. Protein damage and degradation by oxygen radicals. I. General aspects. J Biol Chem. 1987;262:9895–901.

    Google Scholar 

  24. Rice-Evans C, Burdon R. Free radical-lipid interactions and their pathological consequences. Prog Lipid Res. 1993;32:71−110.

    Article  PubMed  Google Scholar 

  25. Beckman KB, Ames BN. Oxidative decay of DNA. J Biol Chem. 1997;272:19633–6.

    Article  CAS  PubMed  Google Scholar 

  26. Squadrito GL, Pryor WA. Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic Biol Med. 1998;25:392–403.

    Article  CAS  Google Scholar 

  27. Virag L, Szabo E, Bakondi E, Bai P, Gergely J, Hunyadi J, Szabo C. Nitric oxide-peroxynitrite-poly (ADP-ribose) polymerase pathway in the skin. Exp Dermatol. 2002;11:189–202.

    Article  CAS  PubMed  Google Scholar 

  28. Sinet PM, Heikkila RE, Cohen G. Hydrogen peroxide production in rat brain in vivo. J Neurochem. 1980;34:1421−8.

    Article  PubMed  Google Scholar 

  29. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J. 1995;9:526−33.

    PubMed  Google Scholar 

  30. Chan PH. Role of oxidants in ischemic brain damage. Stroke. 1996;27:1124−9.

    PubMed  Google Scholar 

  31. Raps SP, Lai JCK, Hertz I, Cooper AJL. Glutathione is present in high concentration in cultured astrocytes but not in cultured neurons. Brain Res. 1989;493:398−401.

    Article  PubMed  Google Scholar 

  32. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989;86:6377−81.

    Article  PubMed  Google Scholar 

  33. Brodie BB, Axelrode J, Shore PA, Udenfriend S. Ascorbic acid in aromatic hydroxylation. II. Products formed by reaction of substrates with ascorbic acid, ferrous ion, and oxygen. J Biol Chem. 1954;208:741−50.

    PubMed  Google Scholar 

  34. Halliwell B. Vitamin C: antioxidant or prooxidant in vivo. Free Radic Res. 1996;25:439−54.

    PubMed  Google Scholar 

  35. Boldyrev AA, Dupin A, Bunin YA, Babizhaev MA, Severin E. The antioxidative properties of carnosine, a natural histidine containing dipeptide. Biochem Int. 1987;15:1105−13.

    PubMed  Google Scholar 

  36. Tabakman R, LazaroviciP, Kohen R. Neuroprotective effects of carnosine and homocarnosine on pheochromocytoma PC12 cells exposed to ischemia. J Neurosci Res. 2002;68:463–9.

    Article  CAS  PubMed  Google Scholar 

  37. Kalyankar G, Meister A. Enzymatic synthesis of carnosine and related β-alanyl and γ-aminobutyryl peptides. J Biol Chem. 1959;234:3210–8.

    CAS  PubMed  Google Scholar 

  38. Horinishi H, Grillo M, Margolis FL. Purification and characterization of carnosine synthetase from mouse olfactory bulbs. J Neurochem. 1978;31:909–19.

    Article  CAS  PubMed  Google Scholar 

  39. Boldyrev AA. Does carnosine possess direct antioxidant activity? Int J Biochem. 1993;25:1101–7.

    Article  CAS  PubMed  Google Scholar 

  40. Boldyrev AA, Stvolinsky SL, Tyulina OV, Koshelev VB, Hori N, Carpenter DO. Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol. 1997;17:259–70.

    Article  CAS  PubMed  Google Scholar 

  41. Boldyrev AA, Johnson P, Wei Y, Tan Y, Carpenter DO. Carnosine and taurine protect rat cerebellar granular cells from free radical damage. Neurosci Lett. 1999;263:169–72.

    Article  CAS  PubMed  Google Scholar 

  42. Kohen R, Misgav R, Ginsburg I. The SOD like activity of copper:carnosine, copper:anserine and copper:homocarnosine complexes. Free Radic Res Commun. 1991;12–13(pt 1):179–85.

    Article  PubMed  Google Scholar 

  43. Pozo D, Reiter RJ, Calvo JR, Guerrero JM. Physiological concentration of melatonin inhibits nitric oxide synthase in rat cerebellum. Life Sci. 1994;55:455−60.

    Article  Google Scholar 

  44. Wayner DDM, Burton GW, Ingold KU, Barclay LC, Locke SJ. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochem Biophys Acta. 1987;924:408−19.

    PubMed  Google Scholar 

  45. Benzie IFF, Strain JJ. Uric acid: friend or foe? Redox Rep. 1996;2:231−4.

    Google Scholar 

  46. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981;73:6858−62.

    Google Scholar 

  47. Davies KA, Sevanian A, Muallassah-Kelly F, Hochstein P. Uric acid-iron complexes. Biochem J. 1986;235:747−4.

    Google Scholar 

  48. Sevanian A, Davies KJA, Hochstein P. Serum urate as an anti-oxidant for ascorbic acid. Am J Clin Nutr. 1991;54:1129S−34S.

    Google Scholar 

  49. Glantz L, Avramovich A, Trembovler V, Gurvitz V, Kohen R, Eidelman LA, Shohami E. Ischemic preconditioning increases antioxidants in the brain and peripheral organs after cerebral ischemia. Exp Neurol. 2005;192:117–24.

    Article  CAS  PubMed  Google Scholar 

  50. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995;19:227−50

    Article  PubMed  Google Scholar 

  51. Packer L, Tritschler H, Wessel K. Neuroprotection by the metabolic antioxidant α-lipoic acid. Free Radic Biol Med. 1997;22:359−78.

    Article  PubMed  Google Scholar 

  52. Nicholls DG, Ward MW. Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts. Trends Neurosci. 2000;23:166–74.

    Article  CAS  Google Scholar 

  53. Sullivan PG, Thompson MB, Scheff SW. Cyclosporin A attenuates acute mitochondrial dysfunction following traumatic brain injury. Exp Neurol. 1999;160:226–34.

    Article  CAS  PubMed  Google Scholar 

  54. Singh IN, Sullivan PG, Deng Y, Mbye LH, Hall ED. 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. 2006;26:1407–18.

    Article  CAS  PubMed  Google Scholar 

  55. Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? J Neurosci Res. 2005;79:231–9.

    Article  CAS  PubMed  Google Scholar 

  56. Beit-Yannai E, Kohen R, Horowitz M, Trembovler V, Shohami E. Changes in biological reducing activity in rat brain following closed head injury: a cyclic voltammetry study in normal and acclimated rats. J Cereb Blood Flow Metabol. 1997;17:273–9.

    CAS  Google Scholar 

  57. Beckman JS. The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J Dev Physiol. 1991;15:53–9.

    CAS  PubMed  Google Scholar 

  58. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 1991;91:14S–22S.

    Article  CAS  PubMed  Google Scholar 

  59. Mattson MP. Modification of ion homeostasis by lipid peroxidation: roles in neuronal degeneration and adaptive plasticity. Trends Neurosci. 1998;21:53–7.

    Article  CAS  PubMed  Google Scholar 

  60. Khaldi A, Chiueh CC, Bullock MR, Woodward JJ. The significance of nitric oxide production in the brain after injury. Ann N Y Acad Sci. 2002;962:53–9.

    Article  CAS  PubMed  Google Scholar 

  61. Cherian L, Hlatky R, Robertson CS. Nitric oxide in traumatic brain injury. Brain Pathol. 2004;14:195–201.

    Article  CAS  PubMed  Google Scholar 

  62. Darwish RS, Amiridze N, Aarabi B. Nitrotyrosine as an oxidative stress marker: evidence for involvement in neurologic outcome in human traumatic brain injury. J Trauma. 2007;63:439–42.

    Article  PubMed  Google Scholar 

  63. Bard AJ, Faulkner LR. Electrochemical methods: fundamentals and application, vol. 9. New York: Wiley; 1980, p. 316–69.

    Google Scholar 

  64. Beit-Yannai E, Zhang R, Trembovler V, Samuni A, Shohami E. Cerebroprotective effect of stable nitroxide radicals in closed head injury in the rat. Brain Res. 1996;717:22–8.

    Article  CAS  PubMed  Google Scholar 

  65. Elangovan V, Kohen R, Shohami E. Neurological recovery from closed head injury is impaired in diabetic rats. J. Neurotrauma. 2000;17:1013–27.

    Article  CAS  PubMed  Google Scholar 

  66. Chen Y, Lomnitski L, Michaelson DM, Shohami E. Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury. Neuroscience. 1997;80:1255–62.

    Article  CAS  PubMed  Google Scholar 

  67. Lomnitski L, Kohen R, Chen Y, Shohami E, Vogel T, Michaelson DM. Reduced levels of antioxidants in brain of apolipoprotein E deficient mice, following closed head injury. Pharmacol Biochem Behav. 1997;57:669–73.

    Article  Google Scholar 

  68. Reiter RJ. The role of the neurohormone melatonin as a buffer against macromolecular oxidative damage. Neurochem Int. 1995;27:453–60.

    Article  CAS  PubMed  Google Scholar 

  69. Beni SM, Kohen R, Reiter RJ, Tan D-X, Shohami E. Melatonin-induced neuroprotection after closed head Injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-κB and AP-1. FASEB J. 2004;18:149–51.

    CAS  PubMed  Google Scholar 

  70. Shohami E, Gati I, Beit-Yannai E, Trembovler V, Kohen R. Closed head injury in the rat induces whole body oxidative stress: overall reducing antioxidant profile. J Neurotrauma. 1999;16:365–76.

    Article  CAS  PubMed  Google Scholar 

  71. Nickander KK, Schmelzer JD, Rohwer DA, Low PA. Effect of tocopherol deficiency on indices of oxidative stress in normal and diabetic peripheral nerve. J Neurol Sci. 1994;126:6–14.

    Article  CAS  PubMed  Google Scholar 

  72. Cotter MA, Love A, Watt MJ, Cameron NE, Dines KC. Effect of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats. Diabetologia. 1995;38:1285–94.

    Article  CAS  PubMed  Google Scholar 

  73. Davis M, Mendelow AD, Perry RH, Chambers IR, James OF. Experimental stroke and neuroprotection in the aging rat brain. Stroke. 1995;26:1072–8.

    CAS  PubMed  Google Scholar 

  74. Armstead WM. Age dependent NMDA contribution to impaired hypotensive cerebral hemodynamics following brain injury. Brain Res Dev Brain Res. 2002;139:19–28.

    Article  CAS  PubMed  Google Scholar 

  75. Bashore TR, Ridderinkhof KR. Older age, traumatic brain injury, and cognitive slowing: some convergent and divergent findings. Psychol Bull. 2002;128:151–98.

    Article  PubMed  Google Scholar 

  76. Goldstein FC, Levin HS. Cognitive outcome after mild and moderate traumatic brain injury in older adults. J Clin Exp Neuropsychol. 2001;23:739–53.

    Article  CAS  PubMed  Google Scholar 

  77. Butterfield D, Drake J, Pocernich C, Castenga A. Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med. 2001;7:548–54.

    Article  CAS  PubMed  Google Scholar 

  78. Esposito E, Rotilio E, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging. 2002;23:719–35.

    Article  CAS  PubMed  Google Scholar 

  79. Maier CM, Chan PH. Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Neuroscientist. 2002;8:323–34.

    Article  CAS  PubMed  Google Scholar 

  80. Harman D. Aging: theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300.

    CAS  PubMed  Google Scholar 

  81. Joseph JA, Denisova NA, Bielinski D, Fisher DR, Shukkit-Hale B. Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention. Mech Ageing Dev. 2000;116:141–53.

    Article  CAS  PubMed  Google Scholar 

  82. Moor E, Shohami E, Kanevsky E, Grigoriadis N, Symeonidou C, Kohen R. Impairment of the ability of the injured aged brain in elevating urate and ascorbate. Exp Gerontol. 2006;41:303–11.

    Article  CAS  PubMed  Google Scholar 

  83. Fridovich I. Superoxide dismutases. Annu Rev Biochem. 1975;44:147–59.

    Article  CAS  PubMed  Google Scholar 

  84. Huang CY, Fujimura M, Noshita N, Chang YY, Chan PH. SOD1 down-regulates NF-kappaB and c-Myc expression in mice after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2001;21:163–73.

    Article  CAS  PubMed  Google Scholar 

  85. Chan PH, Yang GY, Chen SF, Carlson E, Epstein CJ. Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase. Ann Neurol. 1991;29:482–6.

    Article  CAS  PubMed  Google Scholar 

  86. Lewen A, Sugawara T, Gasche Y, Fujimura M, Chan PH. Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury. Neurobiol Dis. 2001;8:380–90.

    Article  CAS  PubMed  Google Scholar 

  87. Mikawa S, Kinouchi H, Kamii H, Gobbel GT, Chen SF, Carlson E, Epstein CJ, Chan PH. Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice. J Neurosurg. 1996;85:885–91

    Article  CAS  PubMed  Google Scholar 

  88. Chan PH, Kawase M, Murakami K, Chen SF, Li Y, Calagui B, Reole L, Carlson E, Epstein CJ. Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion. J Neurosci. 1998;18:8292–9.

    CAS  PubMed  Google Scholar 

  89. Murakami K, Kondo T, Epstein CJ, Chan PH. Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice. Stroke. 1997;28:1797–804.

    CAS  PubMed  Google Scholar 

  90. Yang GY, Chan P, Chen J, Carlson E, Chen SF, Weinstein P, Epstein CJ, Kamii H. Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke. 1994;25:165–70.

    PubMed  Google Scholar 

  91. Fujimura M, Morita-Fujimura Y, Copin J, Yoshimoto T, Chan PH. Reduction of copper, zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia. Brain Res. 2001;889:208–13.

    Article  CAS  PubMed  Google Scholar 

  92. Kelner MJ, Bagnell R, Montoya M, Estes L, Uglik SF, Cerutti P. Transfection with human copper-zinc superoxide dismutase induces bidirectional alterations in other antioxidant enzymes, proteins, growth factor response, and paraquat resistance. Free Radic Biol Med. 1995;18:497–506.

    Article  CAS  PubMed  Google Scholar 

  93. Peled-Kamar M, Lotem J, Wirguin I, Weiner L, Hermalin A, Groner Y. Oxidative stress mediates impairment of muscle function in transgenic mice with elevated level of wild-type Cu/Zn superoxide dismutase. Proc Natl Acad Sci U S A. 1997;94:3883–7.

    Article  CAS  PubMed  Google Scholar 

  94. Gahtan E, Auerbach JM, Groner Y, Segal M. Reversible impairment of long-term potentiation in transgenic Cu/Zn-SOD mice. Eur J Neurosci. 1998;10:538–44.

    Article  CAS  PubMed  Google Scholar 

  95. Beni SM, Tsenter J, Alexandrovich AG, Galron-Krool N, Barzilai A, Kohen R, Grigoriadis N, Simeonidou C, Shohami E. CuZn-SOD deficiency, rather than overexpression, is associated with enhanced recovery and attenuated activation of NF-kappaB after brain trauma in mice. J Cereb Blood Flow Metab. 2006; 26:478–90.

    Article  CAS  PubMed  Google Scholar 

  96. de Haan JB, Crack PJ, Flentjar N, Iannello RC, Hertzog PJ, Kola I. An imbalance in antioxidant defense affects cellular function: the pathophysiological consequences of a reduction in antioxidant defense in the glutathione peroxidase-1 (Gpx1) knockout mouse. Redox Rep. 2003;8:69–79.

    Article  CAS  PubMed  Google Scholar 

  97. Rodriguez AM, Carrico PM, Mazurkiewicz JE, Melendez JA. Mitochondrial or cytosolic catalase reverses the MnSOD-dependent inhibition of proliferation by enhancing respiratory chain activity, net ATP production, and decreasing the steady state levels of H2O2. Free Radic Biol Med. 2000;29:801–13

    Article  Google Scholar 

  98. Xiong Y, Shie F-S, Zhang J, Lee C-P, Ho Y-S. The protective role of cellular glutathione peroxidase against trauma-induced mitochondrial dysfunction in the mouse brain. J Stroke Cereb Dis. 2004;13:129–37.

    Article  Google Scholar 

  99. Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J. 1988;2:2557–68.

    CAS  PubMed  Google Scholar 

  100. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997;37:517–54.

    Article  CAS  PubMed  Google Scholar 

  101. McCoubrey WK Jr, Maines MD. The structure, organization and differential expression of the gene encoding rat heme oxygenase-2. Gene. 1994;139:155–61.

    Article  Google Scholar 

  102. Maines MD, Eke BC, Zhao X. Corticosterone promotes increased heme oxygenase-2 protein and transcript expression in the newborn rat brain. Brain Res. 1996;722:83–94.

    Article  CAS  PubMed  Google Scholar 

  103. Chang EF, Wong RJ, Vreman HJ, Igarashi T, Galo E, Sharp FR, Stevenson DK, Noble-Haeusslein1 LJ. Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury. J Neurosci. 2003;23:3689–96.

    CAS  PubMed  Google Scholar 

  104. Hillered L, Kotwica Z, Ungerstedt U. Interstitial and cerebrospinal fluid levels of energy-related metabolites after middle cerebral artery occlusion in rats. Res Exp Med (Berl). 1991;191:219–25.

    Article  CAS  Google Scholar 

  105. Solaroglu I, Okutan O, Kaptanoglu E, Beskonakli E, Kilinc K. Increased xanthine oxidase activity after traumatic brain injury in rats. J Clin Neurosci. 2005;12:273–75.

    Article  CAS  Google Scholar 

  106. Ankel EG, Lai CS, Hopwood LE, Zivkovic Z. Cytotoxicity of commonly used nitroxide radical spin probes. Life Sci. 1987;40:495–8.

    Article  CAS  PubMed  Google Scholar 

  107. Berliner JL, Fujii H. Magnetic resonance imaging of biological specimens by electron paramagnetic resonance of nitroxide spin labels. Science. 1985;227:517–9.

    Article  CAS  PubMed  Google Scholar 

  108. Krishna MC, Russo A, Mitchell JB, Goldstein S, Dafni H, Samuni A. Do nitroxide antioxidants act as scavengers of O2 –. or as SOD mimics? J Biol Chem. 1996;271:26026–31.

    Article  CAS  PubMed  Google Scholar 

  109. Samuni A, Krishna CM, Mitchell JB, Collins CR, Russo A. Superoxide reaction with nitroxides. Free Radic Res Commun. 1990;9:241–9.

    Article  CAS  PubMed  Google Scholar 

  110. Samuni A, Mitchell JB, DeGraff W, Krishna CM, Samuni U, Russo A. Nitroxide SOD-mimics: modes of action. Free Radic Res Commun. 1991;12–13:187–94.

    Article  PubMed  Google Scholar 

  111. Zhang R, Shohami E, Beit-Yannai E, Bass R, Trembovler V, Samuni A. Mechanism of brain protection by nitroxide radicals in experimental model of closed head injury. Free Radic Biol Med. 1998;24:332–40.

    Article  CAS  PubMed  Google Scholar 

  112. McDonald MC, Zacharowski K, Bowes J, Cuzzocrea S, Thiemermann C. Tempol reduces infarct size in rodent models of regional myocardial ischemia and reperfusion. Free Radic Biol Med. 1999;27:493–503.

    Article  CAS  PubMed  Google Scholar 

  113. Hahn SM, Tochner Z, Krishna CM, Glass J, Wilson L, Samuni A, Sprague M, Venzon D, Glatstein E, Mitchell JB, et al. Tempol, a stable free radical, is a novel murine radiation protector. Cancer Res. 1992;52:1750–3.

    CAS  PubMed  Google Scholar 

  114. DeGraff WG, Krishna MC, Russo A, Mitchell JB. Antimutagenicity of a low molecular weight superoxide dismutase mimic against oxidative mutagens. Environ Mol Mutagen. 1992;19:21–6.

    Article  CAS  PubMed  Google Scholar 

  115. Mota-Filipe H, McDonald MC, Cuzzocrea S, Thiemermann C. A membrane-permeable radical scavenger reduces the organ injury in hemorrhagic shock. Shock. 1999;12:255–61.

    Article  CAS  PubMed  Google Scholar 

  116. Leker RR, Teichner A, Lavie G, Shohami E, Lamensdorf I, Ovadia H. The nitroxide antioxidant tempol is cerebroprotective against focal cerebral ischemia in spontaneously hypertensive rats. Exp Neurol. 2002;176:355–63.

    Article  CAS  PubMed  Google Scholar 

  117. Hall ED, Pazara KE, Braughler JM. Effect of tirilazad mesylate on postischaemic brain lipid peroxidation and recovery of extracellular calcium in gerbils. Stroke. 1991;22:361–6.

    CAS  PubMed  Google Scholar 

  118. Hall ED, Yonkers PA, Andrus PK, Cox JW, Anderson DK. Biochemistry and pharmacology of lipid antioxidants in acute brain and spinal cord injury. J Neurotrauma. 1992;9:425–42.

    Article  Google Scholar 

  119. Hall ED, Yonkers PA, Horan KL, Braughler JM. Correlation between attenuation of post-traumatic spinal cord ischaemia and preservation of vitamin E by the 21-aminosteroid U-74006: evidence for an in vivo antioxidant effect. J Neurotrauma. 1989;6:169–76.

    Article  CAS  PubMed  Google Scholar 

  120. Braughler JM, Pregenzer JF. The novel 21-aminosteroid inhibitors of lipid peroxidation: reaction with lipid peroxyl and phenoxyl radicals. Free Radic Biol Med. 1989;7:125–30.

    Article  CAS  PubMed  Google Scholar 

  121. Hall ED, Yonkers PA, McCall JM, Braughler JM. Effects of the 21-aminosteroid U-74006 on experimental head injury in mice. J Neurosurg. 1988;68:456–61.

    Article  CAS  PubMed  Google Scholar 

  122. Raub TJ, Barsuhn CL, Williams LR, Decker DE, Sawada GA, Ho NF. Use of a biophysical-kinetic model to understand the roles of protein binding and membrane partitioning on passive diffusion of highly lipophilic molecules across cellular barriers. J Drug Target. 1993;1:269–86.

    Article  CAS  PubMed  Google Scholar 

  123. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, et al. Clinical trials in head injury. J Neurotrauma. 2002;19:503–57.

    Article  PubMed  Google Scholar 

  124. Empey PE, McNamara PJ, Young B, Rosbolt MB, Hatton J. Cyclosporin A disposition following acute traumatic brain injury. J Neurotrauma. 2006;23:109–16.

    Article  PubMed  Google Scholar 

  125. Watson BD. Evaluation of the concomitance of lipid peroxidation in experimental models of cerebral ischemia and stroke. Prog Brain Res. 1993;96:69−95.

    Google Scholar 

  126. Stadtman ER. Protein oxidation and aging. Science. 1992;257:1220−4.

    Article  PubMed  Google Scholar 

  127. Ames BN, Shigenaga MT, Hagen M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90:7915−22.

    Article  PubMed  Google Scholar 

  128. Richeson CE, Mulder P, Bowry VW, Ingold KU. The complex chemistry of peroxynitrite decomposition: new insight. J Am Chem. 1998;120:7211–9.

    Article  CAS  Google Scholar 

  129. Kavanagh RJ, Kam PCA. Lazaroids: efficacy and mechanism of action of the 21-aminosteroids in neuroprotection. Br J Anaesth. 2001;86:110–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was partially supported the Israel Science Foundation, (grant no. 241/04). E.S. and R.K. are affiliated with the David R. Bloom Center of Pharmacy and the Dr. Adolph and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics, of the Hebrew University, Jerusalem. E.S. is the incumbent of the Dr. Leon and Dr. Mina Deutsch Chair in Psychopharmacology, and R.K. is the incumbent of the Richard and Jean Zarbin Chair in Medical Studies, at the Hebrew University, Jerusalem.

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  1. Department of Pharmacology, The Hebrew University School of Pharmacy, Jerusalem, Israel

    Esther Shohami

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  1. Esther Shohami
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  2. Ron Kohen
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Correspondence to Esther Shohami .

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  1. Medical School, Dept. Neurology, Tel Aviv University, Tel Aviv, 69978, Israel

    Natan Gadoth

  2. Neurochirurgische Klinik, Abt. Neuropathologie, Universitätsklinikum Mainz, Langenbeckstr. 1, Mainz, 55131, Germany

    Hans Hilmar Göbel

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Shohami, E., Kohen, R. (2011). The Role of Reactive Oxygen Species in the Pathogenesis of Traumatic Brain Injury. In: Gadoth, N., Göbel, H. (eds) Oxidative Stress and Free Radical Damage in Neurology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60327-514-9_7

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