Review of oxidative stress in brain and spinal cord injury: Suggestions for pharmacological and nutritional management strategies

Journal of Spinal Cord Medicine

Volumn 21, Issue 4, 1998, Pages 309-334

  Juurlink, Bernhard H J ^a   Paterson, Phyllis G ^b  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

^b UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

Free radical; Glutathione; Glutathione peroxidase; L 2 oxothiazolidine 4 carboxylate; Lipid peroxidation; N acetylcysteine

Indexed keywords

FREE RADICAL; GLUTAMATE RECEPTOR; REACTIVE OXYGEN METABOLITE;

BRAIN INJURY; DRUG EFFECT; HUMAN; LIPID PEROXIDATION; METABOLISM; NUTRITIONAL SUPPORT; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SPINAL CORD INJURY;

BRAIN INJURIES; FREE RADICALS; HUMANS; LIPID PEROXIDATION; NUTRITIONAL SUPPORT; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; RECEPTORS, GLUTAMATE; SPINAL CORD INJURIES;

EID: 0032176882     PISSN: 10790268     EISSN: None     Source Type: Journal    
DOI: 10.1080/10790268.1998.11719540     Document Type: Article

References (286)

1. Highland T, Salciccioli G, Wilson RF. Spinal cord injuries. In; Wilson RF, Walt AJ, eds. Management of trauma: pitfalls and practice. Baltimore; Williams & Wilkins, 1996:203-24.
2. Michael DB, Wilson RF. Head injuries. In; Wilson RF, Walt AJ, eds. Management of trauma: pitfalls and practice. Baltimore; Williams & Wilkins, 1996:173-202.
3. Isaac L, Pejic L. Secondary mechanisms of spinal cord injury. Surg Neurol 1995;43:484-85.
4. Yakovlev AG, Knoblach SM, Fan L, Fox GB, Goodnight R, Faden AI. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J Neurosci 1997;17:7415-24.
5. Shuman SL, Bresnahan JC, Beattie MS. Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J Neurosci Res 1997;50:798-808.
6. Ranter SS, Yum SW, Faden AI. Alteration in extracellular amino acids after traumatic spinal cord injury. Ann Neurol 1990;27:96-99.
7. Liu D, Thangnipon W, McAdoo DJ. Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord. Brain Res 1991 ;547:344-48.
8. Ratan RR, Murphy TH, Baraban JM. Macromolecular synthesis inhibitors prevent oxidative stress-induced apoptosis in embryonic cortical neurons by shunting cysteine from protein synthesis to glutathione. J Neurosci 1994;14:4385-92.
9. Balentine JD. Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 1978;39:236-53.
10. Tator CH, Koyanagi I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg 1997;86:483-92.
11. Goodman JH, Bingham G, Hunt WE. Ultrastructural blood-brain barrier alterations and edema formation in acute spinal cord trauma. J Neurosurg 1976;44:418-424.
12. Barzo P, Marmarou A, Fatouros P, Corwin F, Dunbar J. Magnetic resonance imaging-monitored acute blood-brain barrier changes in experimental traumatic brain injury. J Neurosurg 1996;85:1113-21.
13. Fehlings MG, Tator CH, Linden RD. The relationships among the severity of spinal injury, motor and somatosensory evoked potentials and spinal cord blood flow. ECG Clin Neurophysiol 1989;74:241-59.
14. ZhangY, Hillered L, OlssonY, Holtz A. Time course of energy perturbation after compression trauma to the spinal cord: an experimental study in the rat using microdialysis. Surg Neural 1993;39:297-304.
15. Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros P, Young HF. Ultra-early evaluation of regional cerebral blood flow in severely headinjured patients using xenon-enhanced computerized tomography. J Neurosurg 1992;77:360-68.
16. Siesjö BK, Katsura Kl, Zhao Q, et al. Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. J Neurotrauma 1995;12:943-56.
17. Siesjö BK, Zhao Q, Pahlmark K, Siesjö P, Katsura K, Folbergrova J. Glutamate, calcium and free radicals as mediators of ischémie brain damage. Ann Thorac Surg 1995;59:1316-20.
18. Hossman KA. Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised. Brain Pathol 1994;4:23-36.
19. Sweeney Ml, Yager JY, Walz W, Juurlink BH. Cellular mechanisms involved in brain ischemia. Can J Physiol Pharm 1995;73:1525-35.
20. Juurlink BH, Sweeney Ml. Mechanisms that result in damage during and following cerebral ischemia. Neurosci Biobehav Rev 1997;21:121-28.
21. Smith AJ, McCrerry DB, Bloedal JR, Chou SN. Hyperemia, CO2 responsiveness, and autoregulation in the white matter following experimental spinal cord injury. J Neurosurg 1978;48:239-51.
22. Grace PA. Ischaemia-reperfusion injury. Br J Surg 1994;81:637-47.
23. Chen J, Jin K, Chen M, et al. Early detection of DNA strand breaks in the brain after transient focal ischemia: implications for the role of DNA damage in apoptosis and neuronal cell death. J Neurochem 1997;69:232-45.
24. Chan PH. Oxygen radicals in focal cerebral ischemia. Brain Pathol 1994;4:59-65.
25. Sussman MS, Bulkley GB. Oxygen-derived free radicals in reperfusion injury. Meth Enzymol 1990;186:711-23.
26. Taoka Y, Okajima K, Uchiba M, et al. Reduction of spinal cord injury by administration of iloprost, a stable prostacyclin analog. J Neurosurg 1997;86:1007-11.
27. Taoka Y, Okajima K, Uchiba M, et al. Role of neutrophils in spinal cord injury in the rat. Neurosci 1997;79:1177-82.
28. Springer JE, Azbill RD, Mark RJ, Begley JG, Waeg G, Mattson MP. 4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake. J Neurochem 1997;68:2469-76.
29. Hakim AM. The cerebral ischémie penumbra. Can J Neural Sei 1987;14:557-59.
30. Walz W. Role of astrocytes in the spreading depression signal between the ischémie core and penumbra. Neurosci Biobehav Rev 1997;21:135-42.
31. Siesjö BK. Basic mechanisms of traumatic brain damage. Ann Emerg Med 1993;22:959-69.
32. Katayama Y, MaedaT, Koshinaga M, KawamataT, Tsubokawa T. Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury. Brain Pathol 1995;5:427-35.
33. 2+ exchanger. J Neurosci 1996;16:545-52.
34. Balentine JD. Pathology of experimental spinal cord trauma. II. Ultrastructure of axons and myelin. Lab Invest 1978;39:254-66.
35. Povlishock JT. Pathobiology of traumatically induced axonal injury in animals and man. Ann Emerg Med 1993;22:980-86.
36. Povlishock JT, Jenkins LW. Are the pathobiological changes evoked by traumatic brain injury immediate and irreversible? Brain Pathol !995;5:415-26.
37. Schoepp DD, Conn PJ. Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol Sei 1993;14:13-20.
38. Seeburg PH. The molecular biology of the mammalian glutamate receptor channels. Trends Pharmacol Sei 1993;14:297-303.
39. Mody I, MacDonald JF. NMDA receptor-dependent excitotoxicity: the role of intracellular Ca2+ release. Trends Pharmacol Sei 1995;16:356-59.
40. Morley P, Hogan MJ, Hakim AM. Calcium-mediated mechanisms of ischémie injury and protection. Brain Pathol 1994;4:37.
41. GembaT, OshimaT, Ninomiya M. Glutamate efflux via the reversal of the sodium-dependent glutamate transporter caused by glycolytic inhibition in rat cultured astrocytes. Neurosci 1994;63:789-95.
42. SaidoTC, Sorimachi H, Suzuki K. Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J 1994;8:814-22.
43. Kampfl A, Posmantur RM, Zhao X, Schmutzhard E, Clifton GL, Hayes RL. Mechanisms of calpain proteolysis following traumatic brain injury: implications for pathology and therapy: review and update. J Neurotrauma 1997;14:121-34.
44. Anderson DK, Hall ED. Pathophysiology of spinal cord trauma. Ann Emerg Med 1993;22:987-92.
45. Hall ED, Braughler JM. Free radicals in CMS injury. Res Publ Assoc Res Nerv Ment Dis 1993;71:81-105.
46. Halliwell B, Gutteridge JM. Free radicals in biology and medicine. 2nd ed. Oxford; Clarendon Press, 1989.
47. Fridovich I. Biological effects of the Superoxide radical. Arch Biochem Biophys 1986;247:1-11.
48. Kukreja RC, Kontos HA, Hess ML, Ellis EF. PGH synthesis and lipoxygenase generate Superoxide in the presence of NADH and NADPH. Circ Res 1986;59:612-19.
49. Chanock SJ, el Benna J, Smith RM, Babior BM. The respiratory oxidase burst. J Biol Chem 1994;269:24519-22.
50. Sâez GT, Sâez JR, Vina J. The role of free radicals in the cytotoxicity of cysteine. In; Miquel J, Quintanilha AT, Weber H, eds. CRC handbook of free radicals and antioxidants in biomedicine. Boca Raton, FL; CRC Press, 1991:81-94.
51. Kalyanaraman B. Free radicals from cate-cholamine hormones, neuromelanins and neuro. toxins. In; Miquel J, Quintanilha AT, Weber H, eds. CRC handbook of free radicals and antioxi-dants in biomedicine. Boca Raton, FL; CRC Press, 1989:147-59.
52. Deby C, Goutier R. New perspectives on the biochemistry of Superoxide anion and the efficiency of Superoxide dismutases. Biochem Pharmacol 1990;39:399-405.
53. Katsuki H, Okuda S. Arachidonic acid as a neurotoxic and neutrotropic substance. Prog Neurobiol 1995;46:607-36.
54. Lipton SA, Choi SB, Pan ZH, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitrosocompounds. Nature 1993;364:626-32.
55. Squadrito GL, Pryor WA. The formation of peroxynitrite in vivo from nitric oxide and Superoxide. Chem-Biol Interactions 1995;96:203-06.
56. Steinbeck MJ, Khan AU, Karnovsky MJ. Extracellular production of singlet oxygen by stimulated macrophages quantified using 9,10diphenylanthracene and perylene in a polystyrene film. J Biol Chem 1993;268:15649-54.
57. De Silva DM, Aust SD. Ferritin and ceruloplasmin in oxidative damage: review and recent findings. CanJ Physiol Pharmacol 1993;71:715-20.
58. Funk F, Lenders JP, Crichton RR, Schneider W. Reductive mobilization of ferritin iron. Eur J Biol Chem 1985;152:167-72.
59. Fridovich l. Superoxide radical and Superoxide dismutases. Ann Rev Biochem 1995;64:97-112.
60. Van den Bosch H, Schutgens RB, Wanders RJ, Tager JM. Biochemistry of peroxisomes. Ann Rev Biochem 1992;61:157-97.
61. Beckman JS. Peroxynitrite versus hydroxyl radical: the role of nitric oxide in superoxide-dependent cerebral injury. Ann NY Acad Sei 1994,738:69-75.
62. Yamazaki I, Piette LH. EPR spin-trapping study on the oxidizing species formed in the reaction of ferrous ion with hydrogen peroxide. J Am Chem Soc 1991 ;113:7588-93.
63. Steinbeck MJ, Khan AU, Karnovsky MJ. Intracellular singlet oxygen generation by phagocytosing neutrophils in response to particles coated with a chemical trap. J Biol Chem 1992;267:13425-33.
64. Noronha-Dutra AA, Epperlein MM, Woolf N. Reaction of nitric oxide with hydrogen peroxide to produce potentially cytotoxic singlet oxygen as a model for nitric oxide-mediated killing. FEBS Lett 1993;321:59-62.
65. Di Mascio P, Bechara EJ, Medeiros MH, Briviba K, Sies H. Singlet molecular oxygen production in the reaction of peroxynitrite with hydrogen peroxide. FEBS Lett 1994;355:287-89.
66. Zhang L, Marcillat O, Giulivi C, Ernster L, Davies KJ. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem 1990;265:16330-36.
67. Breen AP, Murphy JA. Reactions of oxyl radicals with DMA. Free Rad Biol Med 1995;18:1033-77.
68. Henle ES, Linn S. Formation, prevention, and repair of DMA damage by iron/hydrogen peroxide. J Biol Chem 1997;272:19095-98.
69. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989;320:365-76.
70. Schraufsratter ID, Browne K, Harris A, et al. Mechanisms of hypochlorite injury of target cells. J Clin Invest 1990;85:554-62.
71. Panasenko OM, Evgina SA, Driomina ES, Sharov VS, Sergienko VI, Vladimirov YA. Hypochlorite induces lipid peroxidation in blood lipoproteins and phospholipid lysosomes. Free Rad Biol Med 1995;19:1330.
72. Khan AU, Kasha M. Singlet molecular oxygen in the Haber-Weiss reaction. Proc Natl Acad Sei USA 1994;91:12365-67.
73. Zhai X, Ashraf M. Direct detection and quantification of singlet oxygen during ischemia and reperfusion in rat hearts. Amer J Physiol 1995;38:H 1229-36.
74. 2+-ATPase of cardiac sarcoplasmic reticulum. Circ Res 1991;69:1003-14.
75. Kukreja RC, Jesse RL, Hess ML. Singlet oxygen: a potential culprit in myocardial injury? Mol Chem Biochem 1992;111:17-24.
76. Michaeli A, Feitelson J. Reactivity of singlet oxygen toward amino acids and peptides. Photochem Photobiol 1994;59:284-89.
77. Michaeli A, Feitelson J. Reactivity of singlet oxygen toward large peptides. Photochem Photobiol 1995;61:255-60.
78. Escobar JA, Robio MA, Lissi EA. SOD and catalase inactivation by singlet oxygen and peroxyl radicals. Free Rad Biol Med 1996;20:285-90.
79. Gorman AA. The bimolecular reactivity of singlet molecular oxygen. Adv Photochem 1992;17:217-74.
80. Tanielian C, Mechin R. Reaction and quenching of singlet molecular oxygen with esters of polyunsaturated fatty acids. Photochem Photobiol 1994;59:263-68.
81. Li Y, Trush MA. Reactive oxygen-dependent DMA damage resulting from the oxidation of phenolic compounds by a copper-redox cycle mechanism. Cancer Res 1994;54:1895-98.
82. DavvsonTM, Snyder SH. Gases as biological mes-sengers: nitric oxide and carbon monoxide in the brain. J Neurosci 1994;! 4:5147-59.
83. Förstermann U, Closs El, Pollock JS, et al. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hyperten 1994;23:1121-31.
84. Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science 1992;258:1898-902.
85. Zhang J, Dawson VL, Dawson TM, Snyder SH. Nitric oxide activation of poly (ADP-ribose) synthetase in neurotoxicity. Science 1994;263:687-89.
86. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and Superoxide. Proc Natl Acad Sei USA 1990;87:1620-24.
87. Crow JP, Spruell C, Chen J, et al. On the pHdependent yield of hydroxyl radical products from peroxynitrite. Free Rad Biol Med 1994;16:331-38.
88. Denicola A, Souza JM, Gatti RM, Augusto O, Radi R. Desferrioxamine inhibition of the hydroxyl radical-like reactivity of peroxynitrite: role of the hydroxamic groups. Free Rad Biol Med 1995;19:11-19.
89. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of Superoxide and nitric oxide. J Biol Chem 1991;266:4244-50.
90. Radi R, Rodriguez M, Castro L, Teilen R. Inhibition of mitochondria! electron transport by peroxynitrite. Arch Biochem Biophys 1994;308:89-95.
91. Douki T, Cadet J. Peroxynitrite mediated oxidation of purine bases of nucleosides and isolated DNA. Free Rad Res 1996;24:369-80.
92. Epe B, Ballmaier D, Roussyn l, Briviba K, Sies H. DNA damage by peroxynitrite characterized with DNA repair enzymes. Nucleic Acid Res 1996;24:4105-10.
93. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of Superoxide and nitric oxide. Arch Biochem Biophys 1991;288:481-87.
94. Rodenas J, Mitjavila MT, Carboneil T. Simultaneous generation of nitric oxide and superoxide by inflammatory cells in rats. Free Rad Biol Med 1995;! 8:869-75.
95. Wallace MN, Bisland SK. NADPH-diaphorase activity in activated astrocytes represents inducible nitric oxide synthase. Neurosci 1994;59:905-19.
96. Bolanos JP, Almeida A, Stewart V, et al. Nitric oxide mediated mitochondrial damage in the brain: mechanisms and implications for neurodegenerative diseases. J Neurochem 1997;68:2227-40.
97. Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol 1993;! 51:2132-41.
98. Bolanos JP, Heales SJ, Land JM, Clark JB. Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J Neurochem 1995;64:1965-72.
99. Choi DW. Nitric oxide: foe or friend to the injured brain? Proc Natl Acad Sei USA 1993;90:9741-43.
100. Braughler JM, Hall ED. Involvement of lipid peroxidation in CNS injury. J Neurotrauma 1992;9:S1-7.
101. Braughler JM, Hall ED. Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free Rad Biol Med 1989;6:289-301.
102. Tretter L, Adam-Vizi V. Early events in free radicalmediated damage of isolated nerve terminals: effects of peroxides on membrane potential and intracellular Na+ and Ca2+ concentrations. J Neurochem 1996;66:2057-66.
103. Rauchova H, Ledvinkova J, Kalous M, Drahota Z. The effect of lipid peroxidation on the activity of various membrane-bound ATPases in rat kidney. Int J Biochem Cell Biol 1995;27:251-55.
104. OhtsukiT, Matsumoto M, Suzuki K, Taniguchi N, KamadaT. Mitochondrial lipid peroxidation and Superoxide dismutase in rat hypertensive target organs. Am J Physiol 1995;268:H1418-21.
105. Sokoloff L. Circulation and energy metabolism of the brain. In; Sigel J, Agranoff BW, Albers RW, Molinoff PB, eds. Basic neurochemistry. New York; Raven Press, 1989:565-90.
106. Bovaris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 1973;134:707-16.
107. 106a. Sawada M, Carlson JC. Changes in Superoxide radical and lipid peroxide formation in the brain, heart and liver during the lifetime of the rat. Mech Aging Devel 1987;41:125-37.
108. BrayTM,Taylor CG. Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochem Pharmacol 1994;47:2113-23.
109. Slivka A, Mytilineou C, Cohen C. Histochemical evaluation of glutathione in brain. Brain Res 1987;409:275-84.
110. Philbert MA, Beiswanger CM, Waters DK, Reuhl KR, Lowndes HE. Cellular and regional distribution of reduced glutathione in the nervous system of the rat: histochemical localization by mercury orange and o-phthaldialdehyde-induced histofluorescence. Toxicol Appl Pharmacol 1991 ;107:215-27.
111. Romero FJ, Monsalve E, Hermenegildo C, et al. Oxygen toxicity in the nervous system: comparison of the antioxidant defense of rat brain and sciatic nerve. Neurochem Res 1991 ;16:157-61.
112. Damier P, Hirsch EC, Zhang P, Agid Y, Javoy-Agid F. Glutathione peroxidase, glial cells and Parkinson's disease. Neurosci 1993;52:1-6.
113. Agranoff BW. Lipids. In; Siegel J, Agranoff BW, Albers RW, Molinoff PB, eds. Basic neurochemistry. New York: Raven Press, 1989:91-107.
114. Richter C, Kass GE. Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis, cell death, proliferation, and differentiation. Chem-Biol Interactions 1991;77:1-23.
115. Wei EP, Lamb RG, Kontos HA. Increased phospholipase C activity after brain injury. J Neurosurg 1982;56:695-98.
116. Demediuk P, Saunders RD, Anderson DK, Means ED, Horrocks LA. Membrane lipid changes in laminectomized and traumatized cat spinal cord. Proc Natl Acad Sei USA 1985;82:7071-75.
117. Farooqui AA, Horrocks LA. Involvement of glutamate receptors, Upases, and phospholipases in long-term potentiation and neurodegeneration. J Neurosci Res 1994;38:6-11.
118. Daniel LW. Phospholipases. In; Lands WE, ed. Biochemistry of arachidonic acid metabolism. Boston; Nijhoff, 1985:175-93.
119. Bazan NG, Deturco EB, Allan G. Mediators of injury in neurotrauma: intracellular signal transduction and gene expression. J Neurotrauma 1995;! 2:791-814.
120. Wahl M, Schilling L, Unterberg A, Baethmann A. Mediators of vascular and parenchymal mechanisms in secondary brain damage. Acta Neurochir 1993;57:64-72.
121. Steinbeck MJ, Hegg GG, Karnovsky MJ. Arachidonate activation of the neutrophil NADPHoxidase. Synergistic effects of protein phosphatase inhibitors compared with protein kinase activators. J Biol Chem 1991 ;266:16336-42.
122. Bates EJ. Eicosanoids, fatty acids and neutrophils: their relevance to the pathophysiology of disease. Prostagland Leukotr Ess Fatty Acids 1955;53:75-86.
123. Henderson WR Jr. The role of leukotrienes in inflammation. Ann Int Med 1994;121:684-97.
124. Dahlen S-E, Björk J, Hedqvist P, et al. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sei USA 1981;78:3887-91.
125. Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991 ;67:1033-36.
126. Hall ED. The neuroprotective pharmacology of methylprednisolone. J Neurosurg 1992;76:13-22.
127. Harrison KA, Murphy RC. Isoleukotrienes are biologically active free radical products of lipid peroxidation. J Biol Chem 1995;270:17273-78.
128. Baker RR. Enzymes of platelet activating factor synthesis in brain. Neurochem Res 1995;20:1345-51.
129. Kubes P. Polymorphonuclear leukocyte - endothelium reactions: a role for pro-inflammatory and anti-inflammatory molecules. Can J Physiol Pharmacol 1993;71:88-97.
130. Stewart AC, Dubbin PN, Harris!, Dusting CJ. Platelet-activating factor may act as a second messenger in the release of icosanoids and Superoxide anions from leukocytes and endothelial cells. Proc Natl Acad Sei USA 1990;87:3215-19.
131. Nogami K, HirashimaY, Endo S, Takaku A. Involvement of platelet-activating factor (PAF) in glutamate neurotoxicity in rat neuronal cultures. Brain Res 1997;754:72-78.
132. Shiga Y, Onodera H, Kogure K, et al. Neutrophil as a mediator of ischémie edema formation in the brain. Neurosci Lett 1991;!25:110-12.
133. Yamasaki Y, Matsuura N, Shozuhara H, Onodera H, Itoyama Y, Kogure K. lnterleukin-1 as a pathogenic mediator of ischémie brain damage in rats. Stroke 1995;26:676-80.
134. Jiang N, Moyle M, Soûle HR, Rote WE, Chopp M. Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats. Ann Neurol 1995;38:935-42.
135. MatsuoY, KihariT, Ikeda M, Ninomiya M, Onodera H, Kogure K. Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain. Brain Res 1996;709:296-302.
136. Lindsberg PJ, Siren AL, Feuerstein GZ, Hallenbeck JM. Antagonism of neutrophil adherence in the deteriorating stroke model in rabbits. J Neurosurg 1995;82:269-77.
137. Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Ann Rev Pharmacol Toxicol 1993;33:71-79.
138. Shohami E, Novikov M, Bass R, Yamin A, Gallily R. Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue. J Cereb Blood Flow Metabl994;14:615-19.
139. Shohami E, Bass R, Wallach D, Yamin A, Gallily R. Inhibition of tumor necrosis factor alpha (TNFalpha) activity in rat brain is associated with cerebroprotection after closed head injury. J Cereb Blood Flow Metab 1996;16:378-84.
140. Hirschberg DL, Yoles E, Belkin M, Schwartz M. Inflammation after axonal injury has conflicting consequences for recovery of function: rescue of spared axons is impaired but regeneration is supported. J Neuroimmunol 1994;50:9-16.
141. KondoT, ReaumeAG, HuangTT, et al. Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J Neurosci 1997;17:4180-89.
142. Chan PH, Epstein CJ, Li Y, et al. Transgenic mice and knockout mutants in the study of oxidative stress in brain injury. J Neurotrauma 1995;12:815-24.
143. Francis JW, Ren JM, Warren L, Brown RH Jr, Finkelstein SP. Postischemic infusion of Cu/Zn Superoxide dismutase or SOD: Tet451 reduces cerebral infarction following focal ischemia/reperfusion in rats. Exp Neural 1997;146:435-43.
144. Muizelaar JP, Marmarou A, Young HF, et al. Improving the outcome of severe head injury with oxygen radical scavenger polyethylene glycol-conjugated Superoxide dismutase: a phase II trial. J Neurosurg 1993;78:375-82.
145. Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA. Detection of catalase in rat heart mitochondria. J Biol Chem 1991;266:22028-34.
146. Radi R, Bush KM, Freeman BA. The role of cytochrome C and mitochondrial catalase in hydroperoxide-induced heart mitochondrial lipid peroxidation. Arch Biochem Biophys 1993;300:409-15.
147. SimmonsTW, Jamall IS. Significance of alterations in hepatic antioxidant enzymes. Primacy of glutathione peroxidase. Biochem J 1988;251:913-17.
148. Makino N, Mochizuki Y, Bannai S, SugitaY. Kinetic studies on the removal of extracellular hydrogen peroxide by cultured fibroblasts. J Biol Chem 1994;269:1020-25.
149. Floh TL. Glutathione peroxidase: fact and fiction. In; Fridovich I, ed. Oxygen free radicals and tissue damage. Amsterdam; Excerpta Medica, 1979:95-113.
150. Wendel A. Glutathione peroxidase. ln;Jacoby WB, ed. Enzymatic basis of detoxification. New York; Academic Press, 1980:333-53.
151. Maiorino M, Gregolin C, Ursini F. Phospholipid hydroperoxide glutathione peroxidase. Meth Enzymol 1990;! 86:448-53.
152. Thomas JP, Maiorino M, Ursini F, Girotti AW. Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. J Biol Chem 1990;265:454-61.
153. Ursini F, Maiorino M, Gregolin C. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim BiophysActa 1985;839:62-70.
154. Esworthy RS, Chu FF, Geiger P, Girotti AW, Doroshovv JH. Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. Arch Biochem Biophys 1993;307:29-34.
155. Dringen R, Hamprecht B. Involvement of glutathione peroxidase and catalase in the disposal of exogenous hydrogen peroxide by cultured astroglial cells. Brain Res 1997;759:67-75.
156. Michiels C, Raes M, Toussaint O, Remacle J. Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Rad Biol Med 1994;17:23518.
157. Thorburne SK, Juurlink BH. Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. J Neurochem 1996;67:1014-22.
158. Juurlink BH. Type-2 astrocytes have much greater susceptibility to heat stress than type-1 astrocytes. J Neurosci Res 1994;38:196-201.
159. Sagara Jl, Miura K, Bannai S. Maintenance of neuronal glutathione by glial cells. J Neurochem 1993;61:1672-76.
160. Meister A. Glutathione. Ann Rev Biochem 1983;79:711-60.
161. Juurlink BH. NADP-linked isozymes are the major forms of isocitrate dehydrogenase in mouse type-1 like astrocytes. Life Sei 1993;52:1087-90.
162. TabatabaieT, Floyd RA. Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents. Arch Biochim Biophys 1994;314:112-19.
163. Barker JE, Heales SJ, Cassidy A, Bolanos JP, Land JM, Clark JB. Depletion of brain glutathione results in a decrease of glutathione reductase activity: an enzyme susceptible to oxidative stress. Brain Res 1996;716:118-22.
164. Foote CS, Denny RW. Chemistry of singlet oxygen. VII. Quenching by b-carotene. J Am Chem Soc 1968;90:6233-35.
165. Everett SA, Dennis MF, Patel KB, Maddix S, Kundu SC, Wilson RL. Scavenging of nitrogen dioxide, thiyl, and sulfonyl free radicals by the nutritional antioxidant b-carotene. J Biol Chem 1996;271:3988-94.
166. The Alpha-Tocopherol BCCPSG. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl JMed 1994;330:1029-35.
167. Sies H, Stahl W. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants. Am J Clin Nutr 1995;62:S1315-21.
168. Chan AC. Partners in defense, vitamin E and vitamin C. Can J Physiol Pharmacol 1993;71:725-31.
169. Winkler BS, Orselli SM, RexTS. The redox couple between glutathione and ascorbic acid: a chemical and physiological perspective. Free Rad Biol Med 1994;17:333-49.
170. Maiorino M, Coassin M, Roveri A, Ursini F. Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. Lipids 1989;24:721-26.
171. Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 1993;300:535-43.
172. Niki E. Synergistic inhibition of oxidation by vitamin E and vitamin C. In; Chow CK, ed. Cellular antioxidant defense mechanisms. Boca Raton, FL; CRC Press, 1988:111-22.
173. Rose RC, Bode AM. Comments on the glutathione-ascorbic acid redox couple. Free Rad Biol Med 1995;! 8:955-56.
174. Bolanos JP, Heales SJ, Peuchen S, Barker JE, Land JM, Clark JB. Nitric oxide-mediated mitochondrial damage: a potential neuroprotective role for glutathione. Free Rad Biol Med 1996;21:995-1001.
175. Fici GJ, Althaus JS, Von Voigtlander PF. Effects of lazeroids and a peroxynitrite scavenger in a cell model of peroxynitrite toxicity. Free Rad Biol Med 1997;22:223-28.
176. Schoneich C, Dillinger U, von Bruchhausen F, Asmus KD. Oxidation of polyunsaturated fatty acids and lipids through thiyl and sulfonyl radicals: reaction kinetics and influence of oxygen and structure of thiyl radicals. Arch Biochem Biophys 1992;292:456-67.
177. Juurlink BH, Husain J. Hyperthermic injury of oligodendrocyte precursor cells-implications for dysmyelination disorders. Brain Res 1994;641:353-56.
178. Husain J, Juurlink BH. Oligodendroglial precursor cell susceptibility to hypoxia is related to poor ability to cope with reactive oxygen species. Brain Res 1995;698:86-94.
179. Wiedau-Pazos M, Goto JJ, Rabizadeh S, et al. Altered reactivity of Superoxide dismutase in familial amyotrophic lateral sclerosis. Science 1996;271:515-18.
180. American Institute for Cancer Research. Dietary phytochemicals in cancer prevention and treatment. New York; Plenum, 1996.
181. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 1983;32:1141-48.
182. Saija A, Scalese M, Lanza M, Marzulla D, Bonina F, Castelli F. Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Rad Biol Med 1995;19:481-86.
183. Van Acker SA, van den Berg DJ, Tromp MN, et al. Structural aspects of antioxidant activity of flavonoids. Free Rad Biol Med !996;20:331-42.
184. Nanjo F, Goto K, Seto R, Suzuki M, Sakai M, Hara Y. Scavenging effects of tea catechins and their derivatives on 1,l-diphenyl-2-picrylhydrazyl radical. Free Rad Med Biol 1996;21:895-902.
185. Tournaire C, Croux S, Maurette MT, et al. Antioxidant activity of flavonoids: efficiency of singlet oxygen (1 delta g) quenching. J Photochem Photobiol B 1993;!9:205-15.
186. Middleton E Jr, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 1992;43:1167-79.
187. Gerritsen ME, Carley WW, Ranges CE, et al. Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. Am J Pathol 1995;! 47:278-92.
188. Sanhueza J, Valdes J, Campos R, Garrido A, Valenzuela A. Changes in the xanthine dehydrogenase/xanthine oxidase ratio in the rat kidney subjected to ischemia-reperfusion stress: preventive effect of some flavonoids. Res Commun Chem Pathol Pharmacol 1992;78:211-18.
189. Pietri S, Seguin JR, d'Arbigny P, Drieu K, Culcasi M. Ginkgo biloba extract (Egb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery. Cardiovasc Drug Ther 1997;11:121-31.
190. Delbarre B, Delbarre G, Calinon F. Effect of Daflon 500 mg, a flavonoid drug, on neurological signs, levels of free radicals and electroretinogram in the gerbil after ischemia-reperfusion injury. Int J Microcirc Clin Exp 1995;! 5:27-33.
191. Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun 1997;236:591-93.
192. Laughton MJ, Evans PJ, Moroney MA, Hoult JR, Halliwell B. Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phe-olic dietary additives. Relationship of antioxidant activity to iron ion-reducing ability. Biochem Pharmacol 1991 ;42:1673-81.
193. MclntoshTK. Novel pharmacologie therapies in the treatment of experimental traumatic brain injury: a review. J Neurotrauma 1993;10:215-61.
194. Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonis drugs. Stroke 1995;26:503-13.
195. Hall ED, Andrus PK, Yonkers PA, et al. Generation and detection of hydroxyl radical following experimental head injury. Ann NY Acad Sei 1994;738:15-24.
196. Hall ED, BraughlerJM. Central nervous system trauma and stroke. II. Physiological and pharmacological evidence for involvement of oxygen radicals and lipid peroxidation. Free Rad Biol Med 1989;6:303-13.
197. Althaus JS, Andrus PK, Williams CM, Von Voightlander PF, Cazers AR, Hall ED. The use of salicylate hydroxylation to detect hydroxyl radical generation in ischémie and traumatic brain injury. Reversal by tirilazad mesylate (U-74006F). Mol Chem Neuropathol 1993;20:147-62.
198. Globus MY, Alonso O, Dietrich WD, Busto R, Ginsberg MD. Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem 1995;65:1704-11.
199. Bracken MB, Shepard MJ, HolfordTR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. J Am Med Assoc 1997;277:1597-1604.
200. Yoshida N, Yoshikawa T, Nakamura Y, et al. Methylprednisolone inhibits neutrophil-endothilial cell interactions induced by interleukin-1beta under flow conditions. Life Sei 1997;60:2341-47.
201. Brandt MM, Lynam E, Sklar LA. Methylprednisolone inhibits three classes of neutrophil receptors in human blood in vitro. J Surg Res1993;55:632-39.
202. Banik NL, Matzelle D, Terry E, Hogan EL. A new mechanism of methylprednisolone and other corticosteroids action demonstrated in vitro: inhibition of a proteinase (calpain) prevents myelin and cytoskeletal protein degradation. Brain Res 1997;748:205-10.
203. Twyman D. Nutritional management of the critically ill neurologic patient. Crit Care Clin 1997;13:39-49.
204. Roberts PR. Nutrition in the head-injured patient. NevvHoriz 1995;3:506-17.
205. Bullock R, Chesnut RM, Clifton G, et al. Nutritional support of brain-injured patients. J Neurotrauma 1996;13:721-29.
206. Grimble RF. Nutritional antioxidants and the modulation of inflammation: theory and practice. New Horiz 1994;2:175-85.
207. Benuck M, Banay-Schwartz M, DeGuzman T, Lajtha A. Effect of food deprivation on glutathione and amino acid levels in brain and liver of young and aged rats. Brain Res 1995;678:259-64.
208. Bauman PF, Smith TK, Bray TM. Effect of dietary protein deficiency and L-2-oxothiazolidine-4-carboxylate on the diurnal rhythm of hepatic glutathione in the rat. J Nutr 1988;118:1048-54.
209. Taylor CG, Bauman PF, Sikorski B, BrayTM. Elevation of lung glutathione by oral supplementation of L-2-oxothiazolidine-4-carboxylate protects against oxygen toxicity in protein-energy malnourished rats. FASEB J 1992;6:3101-07.
210. Morel I, Lescoat G, Cogrel P, et al. Anti-oxidants and iron chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 1993;45:13-19.
211. Norton JA, Ott LG, McClain C, et al. Intolerance to enterai feeding in the brain-injured patient. J Neurosurg 1988;68:62-66.
212. Fürst P. The role of antioxidants in nutritional support. Proc Nutr Soc 1996;55:945-61.
213. Cook NC, Samman S. Flavonoids: chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996;7:66-76.
214. Das NP. Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol 1971;20:3435-45.
215. Hollman PC, de Vries JH, van Leeuwen SD, Megelers MJ, Katan MB. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 1995;62:1276-82.
216. De Vries JH, Janssen PL, Hollman PC, van Staveren WA, Katan MB. Consumption of quercetin and kaempferol in free-living subjects eating a variety of diets. Cancer Lett 1997;114:141-44.
217. Hall ED, Andrus PK, Smith SL, et al. Neuroprotective efficacy of microvescularly-localized versus brain-penetrating antioxidants. Acta Neurochir Suppl 1996;66:107-13.
218. Davvson DA, Masayasu H, Graham DI, Macrae IM. The neuroprotective efficacy of ebselen (a glutathione peroxidase mimic) on brain damage induced by transient focal cerebral ischaemia in the rat. Neurosci Lett 1995;! 85:65-69.
219. Sies H. Ebselen, a selenoorganic compound as glutathione peroxidase mimic. Free Rad Biol Med 1993;14:313-23.
220. Knollema S, Elting JW, Dijkhuizen RM, Nicolay K, Korf J, Terhorst GJ. Ebselen (PZ-51 ) protects the caudata putamen against hypoxia/ischemia induced neuronal damage. Neurosci Res Commun 1996;! 9:47-56.
221. Richman PC, Meister A. Regulation of gammaglutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem 1975;250:1422-26.
222. Deneke SM, Fanburg BL. Regulation of cellular glutathione. Am J Physiol 1989;257:L163-73.
223. Bannai S. Transport of cystine and cysteine in mammalian cells. Biochim Biophys Acta 1984;779:289-306.
224. Deneke SM, Susanto l, Vogel KA, Williams CE, Lawrence RA. Mechanisms of use of extracellular glutathione by lung epithelial cells and pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 1995;12:662-28.
225. Juurlink BH,Thorburne SK, Hertz L. Peroxide scavenging deficit underlies oligodendrocyte susceptibility to oxidative stress. Glia 1998;22:371-78.
226. Hunter EA, Grimble RF. Dietary sulphur amino acid adequacy influences glutathione synthesis and glutathione-dependent enzymes during the inflammatory response to endotoxin and tumor necrosis factor-alpha in rats. Clin Sei 1997;92:297-305.
227. ChungTK, Funk MA, Baker DH. L-2-oxothiazolidine-4-carboxylate as a cysteine precursor: efficacy for growth and hepatic glutathione synthesis in chicks and rats. J Nutr 1990;120:158-65.
228. White RD, Wilson DM, Glosson JA, Madsen DC, Rowe WB, Goldberg DI. Toxicity evaluations of Lcysteine and Procysteine, a cysteine prodrug, given once intravenously to neonatal rats. Toxicol Lett 1993;69:15-24.
229. Anderson ME, Meister A. Intracellular delivery of cysteine. Meth Enzymol 1987;!43:313-25.
230. Harper AE, Benevenga NJ, Wohlhueter RM. Effect of ingestion of disproportionate amounts of amino acids. Physiol Rev 1970;50:428-558.
231. Olney JW. Brain damage and oral intake of certain amino acids. Adv Exp Med Biol 1976;69:497-506.
232. Birnbaum SM, Winitz M, Greenstein JP. Quantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of "non-essential" nitrogen. Arch Biochem Biophys 1957;72:428-36.
233. Olney JW, Ho'OL. Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature 1970;227:609-11.
234. Olney JW, Ho OL, Rhee V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res 1971 ;14:61-76.
235. Karlsen RL, Crofova I, Malthe-Sorenssen D, Fonnum F. Morphological changes in rat brain induced by L-cysteine injection in newborn animals. Brain Res 1981 ;208:167-80.
236. Brandwene EL, Williams SR, Tunget-Johnson C, Turchen SG, Manoguerra AS, Clark RF. Refining the level for anticipated hepatotoxicity in acetaminophen poisoning. J Emerg Med 1996;14:691-95.
237. Speeg KV, Bay MK. Prevention and treatment of drug-induced liver disease. Castro Clin No Amer 1995;24:1047-64.
238. Hazelton GA, Hjelle JJ, Klaassen CD. Effects of cysteine pro-drugs on acetaminophen-induced hepatotoxicity. J Pharmacol ExpTher 1986;237:34119.
239. Grewal KK, Racz WJ. Intracellular calcium disruption as a secondary event in acetaminopheninduced hepatotoxicity. Can J Physiol Pharmacol 1993;71:26-33.
240. Banks MF, Stipanuk MH. The utilization of N-acetylcysteine and L-2-oxothiazolidine-4-carboxylate by rat hepatocytes is limited by their rate of uptake and conversion to cysteine. J Nutr 1994;124:378-87.
241. Flanagan RJ, Meredith TJ. Use of N-acetylcysteine in clinical toxicology. Amer J Med 1991 ;91:131-39.
242. MantTG, Tempowski JH, Volans GN, Talbot JC. Adverse reactions to acetylcysteine and effects of overdose. Br Med J 1984;289:217-23.
243. Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 1988;34:77-82.
244. Knuckey NW, Palm D, Primiano M, Epstein MHY, Johanson CE. N-acetylcysteine enhances hippocampal neuronal survival after transient forebrain ischemia in rats. Stroke 1995;26:305-11.
245. Ellis EF, Dodson LY, Police RJ. Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger N-acetylcysteine following experimental brain injury. J Neurosurg 1991 ;75:774-79.
246. Fukuzawa K, Emre S, Senyuz O, Acarli K, Schvvartz ME, Miller CM. N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia. Transplant 1995;59:6-9.
247. Lehmann D, Karussis D, Misrachi-Koll R, Shezen E, Ovadia H, Abramsky O. Oral administration of the oxidant-scavenger N-acetyl-L-cysteine inhibits acute experimental autoimmune encephalomyelitis. J Neuroimmunol 1994;50:35-42.
248. Kretzschmar M, Klein U, Palutke M, Schirrmeister W. Reduction of ischemia-reperfusion syndrome after abdominal aortic aneurysmectory by Nacetylcysteine but not mannitol. Acta Anaesthesiol Scand 1996;40:657-64.
249. Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med 1995;23:646-51.
250. Spies CD, Reinhart K, Witt I, et al. Influence of Nacetylcysteine on indirect indicators of tissue oxygénation in septic shock patients: results from a prospective, randomized, double-blind study. Crit Care Med 1994;22:17386.
251. Sochman J, Vrbska J, Musilova B, Rocek M. Infarct size limitation: acute N-acetylcysteine defense (ISLAND trial): preliminary analysis and report after the first 30 patients. Clin Cardiol 1996;19:94-100.
252. Bernard GR, Wheeler AP, Arons MM, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. Chest 1997;112:164-72.
253. De Groote J, Van Steenbergen W. Paracetamol intoxication and N-acetyl-cysteine treatment. Acta Gastroent Belg 1995;58:326-34.
254. Williamson JM, Meister A. New substrates of 5oxo-L-prolinase. J Biol Chem 1982;257:12039-42.
255. Williamson JM, Boettcher B, Meister A. Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc Natl Acad Sei USA 1982;79:6246-49.
256. Anderson ME, Meister A. Marked increase of cysteine levels in many regions of the brain after administration of L-2-oxothiazolidine-4-carboxylate. FASEBJ 1989;3:1632-36.
257. Meister A, Anderson ME, Hwang O. Intracellular cysteine and glutathione delivery systems. J Am Coll Nutr 1986;5:137-51.
258. Mesina JE, Page RH, Hetzel FW, Chopp M. Administration of L-2-oxothiazolidine-4-carboxylate increases glutathione levels in rat brain. Brain Res1989;478:181-83.
259. Pileblad E, Magnusson T. Increase in rat brain glutathione following intracerebroventricular administration of gamma-glutamylcysteine. Biochem Pharmacol 1992;44:895-903.
260. Tsan MF, Danis EH, Del Vecchio PJ, Rosano CL. Enhancement of intracellular glutathiqne protects endothelial cells against oxidant damage. Biochem Biophys Res Comm 1985;127:270-76.
261. Luthen R, Grendell JH, Haussinger D, Niederau C. Beneficial effects of L-2-oxothiazolidine-4-carboxylate on cerulein pancreatitis in mice. Castro 1997;112:1681-91.
262. Jain A, Madsen DC, Auld PA, et al. L-2-oxothiazolidine-4-carboxylate, a cysteine precursor, stimulates growth and normalizes tissue glutathione concentrations in rats fed a sulfur amino acid-deficient diet. J Nutr 1995;125:851-56.
263. BrayTM, Taylor CG. Tissue glutathione, nutrition, and oxidative stress. Can J Physiol Pharmacol 1993;71:746-51.
264. Porta P, Aebi S, Summer K, Lauterburg BH. L-2oxothiazolidine-4-carboxylic acid, a cysteine prodrug: pharmacokinetics and effects on thiols in plasma and lymphocytes in human. J Pharmacol ExpTher1991;257:331-34.
265. Kalayjian RC, Skowron C, Emgushov RT, et al. A phase l/ll trial of intravenous L-2-oxothiazolidine4-carboxylic acid (procysteine) in asymptomatic HIV-infected subjects. J AIDS 1994;7:369-74.
266. Fürst P. New parenteral substrates in clinical nutrition. Part I. Introduction. New substrates in protein nutrition. Eur J Clin Nutr 1994;48:607-16.
267. Qi Y, JamindarTM, Dawson G. Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes. J Neurochem 1995;64:2458-64.
268. Klausner RD, Rouault TA, Harford JB. Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 1993;72:19-28.
269. Palmer C, Roberts RL, Bero C. Deferoxamine posttreatment reduces ischémie brain injury in neonatal rats. Stroke 1994;25:1039-45.
270. Hum D, Koehler RC, Blizzard KK, Traystman RJ. Deferoxamine reduces early metabolic failure associated with severe cerebral ischémie acidosis in dogs. Stroke 1995:26:688-95.
271. Panter SS, Braughler JM, Hall ED. Dextran-coupled deferoxamine improves outcome in a murine model of head injury. J Neurotrauma 1992;9:47-53.
272. Bergeron RJ, Brittenham CM. The development of iron chelators for clinical use. Boca Raton, FL; CRC Press, 1994.
273. Voest EE, Vreugdenhil G, Marx JJ. Iron-chelating agents in non-iron overload conditions. Ann Intern Med 1994;120:490-99.
274. Ijichi A, Sakuma S, Tofilon PJ. Hypoxia-induced vascular endothelial growth factor expression in normal rat astrocyte cultures. Glia 1995;14:87-93.
275. Sirois MG, Edelman ER. VEGF effect on vascular permeability is mediated by synthesis of plateletactivating factor. AmJ Physiol 1997;272:2746-56.
276. DiaV-Citrin O, Koren G. Oral iron chelation with deferiprone. Fed Clin N Amer 1997;44:235-47.
277. Rice-Evans CA, Miller NJ, Paganga G. Structureantioxidant activity relationships of flavonoids and the phenolic acids. Free Rad Biol Med 1996;20:933-56.
278. Marcheselli VL, Rossowska MJ, Domingo M-E, Braquet P, Bazan NG. Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. J Biol Chem 1990;265:9140-45.
279. SiminiakT, O'Gorman DJ, Shahi M, Hackett D, Sheridan DJ. Plasma mediated neutrophil stimulation during coronary angioplasty: autocrine effect of platelet activating factor. Br Heart J 1995;74:625-30.
280. Faden AI, Tzendzalian PA. Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma. Am J Physiol 1992;263:909-14.
281. Liu XH, Eun BL, Silverstein FS, Barks JD. The platelet-activating factor antagonist BN 52021 attenuates hypoxic-ischemic brain injury in the immature rat. Ped Res 1996;40:797-803.
282. Kleijnen J, Knipschild P. Ginkgo biloba. Lincet 1992;340:1136-39.
283. Khainaut JF, Tenaillon A, Le Tulzo Y, et al. Plateletactivating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. Grit Care Med 1994;22:1720-28.
284. Brochet B, Guinot P, Orgogozo JM, Confavreux C, Rumbach L, Lavergne V. Double blind placebo controlled multicentre study of ginkgolide B in treatment of acute exacerbations of multiple sclerosis. J Neurol Neurosurg Psychiatr 1995;58:360-62.
285. Ginsberg MD, Pulsinelli WA. The ischémie penumbra, injury thresholds, and the therapeutic window for acute stroke. Ann Neurol 1994;36:553-54.
286. Youssef PP, Cormack J, Evill ÇA, et al. Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the effects of methylprednisolone. Arth Rheum 1996;39:216-25.