Antioxidant defense of the brain: A role for astrocytes

Canadian Journal of Physiology and Pharmacology

Volumn 75, Issue 10-11, 1997, Pages 1149-1163

  Wilson, John X ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

Ascorbate; Central nervous system; Free radicals; Gliosis; Glucose; Glutathione; Ischemia; Neuroprotection; Reactive glia

Indexed keywords

ANTIOXIDANT; ASCORBIC ACID; CATALASE; FREE RADICAL; GLUCOSE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; HYDROXYL RADICAL; OXYGEN RADICAL; SUPEROXIDE DISMUTASE;

ANTIOXIDANT ACTIVITY; ASTROCYTE; BRAIN DISEASE; BRAIN INJURY; CELL RESPIRATION; DEGENERATIVE DISEASE; HUMAN; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; STROKE;

EID: 0031465419     PISSN: 00084212     EISSN: None     Source Type: Journal    
DOI: 10.1139/y97-146     Document Type: Review

References (207)

1. Aas, J., Berg-Johnson, J., Hegstad, E., Laake, J.H., Langmoen, I.A., and Ottersen, O.P. 1995. Redistribution of glutamate and glutamine in slices of human neocortex exposed to combined hypoxia and glucose deprivation. J. Cereb. Blood Flow Metab. 13: 503-515.
2. Andrus, P.K., Fleck, T.J., Oolstveen, J.A., and Hall, E.D. 1997. Neuroprotective effects of the novel brain-penetrating pyrrolopyrimidine antioxidants U-101033E and U-14067F against post-ischemic degeneration of nigrostriatal neurons. J. Neurosci. Res. 47: 650-654.
3. Aschner, M. 1996. The functional significance of brain metallothioneins. FASEB J. 10: 1129-1136.
4. Atabay, C., Cagnoli, C.M., Kharlamov, E., Ikonomovi, M.D., and Manev, H. 1996. Removal of serum from primary cultures of cerebellar granule neurons induces oxidative stress and DNA fragmentation: protection with antioxidants and glutamate receptor antagonists. J. Neurosci. Res. 43: 465-475.
5. Bausch, A.R., and Roy, G. 1996. Volume-sensitive chloride channels blocked by neuroprotective drugs in human glial cells (U-138MG). Glia, 18: 73-77.
6. Beit-Yannai, E., Kohen, R., Horowitz, M., Trembovler, V., and Shohami, E. 1997. Changes of biological reducing activity in rat brain following closed head injury: a cyclic voltametry study in normal and heat-activated rats. J. Cereb. Blood Flow Metab. 17: 273-279.
7. Bell, J.A., Beglan, C.L., and London, E.D. 1996. Interaction of ascorbic acid with the neurotoxic effects of NMDA and sodium nitroprusside. Life Sci. 58: 367-371.
8. Bender, A.S., Young, L.P., and Norenberg, M.D. 1997. Effect of lactic acid on L-glutamate uptake in cultured astrocytes: mechanistic considerations. Brain Res. 750: 59-66.
9. Ben-Yoseph, O., Boxer, P.A., and Ross, B.D. 1996. Assessment of the role of the glutathione and pentose phosphate pathways in the protection of primary cerebrocortical cultures from oxidative stress. J. Neurochem. 66: 2329-2337.
10. Berger, T.M., Polidori, M.C., Dabbagh, A., Evans, P.J., Halliwell, B., Morrow, J.D., Roberts, L.J., II, and Breiz, B. 1997. Antioxidant activity of vitamin C in iron-overloaded human plasma. J. Biol. Chem. 272: 15 656-15 660.
11. Boisvert, D.P., and Hall, E.D. 1996. Tirilazad prevention of reperfusion edema after focal ischemia in cynomolgus monkeys. Can. J. Neurol. Sci. 23: 46-52.
12. Bolanos, J.P., Heales, S.J., Land, J.M., and Clark, J.B. 1995. Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J. Neurochem. 64: 1965-1972.
13. Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., and Lipton, S. 1995. Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide-superoxidase in cortical cell cultures. Proc. Natl. Acad. Sci. U.S.A. 92: 7162-7166.
14. Bonnefoi, M.S. 1992. Mitochondrial glutathione and methyl iodide-induced neurotoxicity in primary neural cell cultures. Neurotoxicology, 13: 401-412.
15. Bowling, A.C., and Beal, M.F. 1995. Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci. 56: 1151-1171.
16. Bridges, R.J., Koh, J., Hatalski, C.G., and Cotman, C.W. 1991. Increased excitotoxic vulnerability of cortical cultures with reduced levels of glutathione. Eur. J. Pharmacol. 192: 199-200.
17. Buettner, G.R., and Jurkiewicz, B.A. 1996. Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat. Res. 145: 52-541.
18. Cafe, C., Torri, C., Bertorelli, L., Tartara, F., Tancioni, F., Gaetani, P., Rodriguez-y-Baena, R., and Marzatico, F. 1995. Oxidative events in neuronal and glial cell-enriched fractions of rat cerebral cortex. Free Radical Biol. Med. 19: 853-857.
19. Cafe, C., Torri, C., Bertorelli, L., Angeretti, N., Lucca, E., Forloni, G., and Marzatico, F. 1996. Oxidative stress after acute and chronic application of β-amyloid fragment 25-35 in cortical cultures. Neurosci. Lett. 203: 61-65.
20. Callahan, D.J., Engle, M.J., and Volpe, J.J. 1990. Hypoxic injury to developing glial cells: protective effect of high glucose. Pediatr. Res. 27: 186-190.
21. Ceruti, S., Barbieri, D., Veronese, E., Cattabeni, F., Cossarizza, A., Giammarioli, A.M., Franceschi, C., and Abbracchio, M.P. 1997. Different pathways of apoptosis revealed by 2-chloro-adenosine and deoxy-D-ribose in mammalian astroglial cells. J. Neurosci. Res. 47: 372-383.
22. Chan, A.C. 1993. Partners in defense, vitamin E and vitamin C. Can. J. Physiol. Pharmacol. 71: 725-731.
23. Chan, P.H. 1996. Role of oxidants in ischemic brain damage. Stroke, 27: 1124-1129.
24. Cho, Y., and Bannai, S. 1990. Uptake of glutamate and cystine in C-6 glioma cells and in cultured astrocytes. J. Neurochem. 55: 2091-2097.
25. Choi, D.W. 1996. Ischemia-induced neuronal apopotosis. Curr. Opin. Neurobiol. 6: 667-672.
26. Ciani, E., Groneng, L., Voltattorni, M., Rolseth, V., Contestabile, A., and Paulsen, R.E. 1996. Inhibition of free radical production or free radical scavenging protects from the excitotoxic cell death mediated by glutamate in cultures of cerebellar granule neurons. Brain Res. 728: 1-6.
27. Clark, W.M., Hazel, J.S., and Coull, B.M. 1995. Lazaroids. CNS pharmacology and current research. Drugs, 50: 971-983.
28. Cowley, D.J., Lukovic, L., and Petty, M.A. 1996. MDL 74,180 reduces cerebral infarction and free radical concentrations in rats subjected to ischaemia and reperfusion. Eur. J. Pharmacol. 298: 227-233.
29. Dalton, T., Pazdernik, T.L., Wagner, J., Samson, F., and Andrews, G.K. 1995. Temporal-spatial patterns of expression of metallothionein-I and -III and other stress related genes in rat brain after kainic acid-induced seizures. Neurochem. Int. 27: 59-71.
30. Daval, J.L., Ghersi-Egea, J.F., Oillet, J., and Koziel, V. 1995. A simple method for evaluation of superoxide radical production in neural cells under various culture conditions: application to hypoxia. J. Cereb. Blood Flow Metab. 15: 71-77.
31. Deliconstantinos, G., and Villiotou, V. 1996. NO synthase and xanthine oxidase activities of rabbit brain synaptosomes: peroxynitrite formation as a causative factor of neurotoxicity. Neurochem. Res. 21: 51-61.
32. Desagher, S., Glowinski, J., and Premont, J. 1996. Astrocytes protect neurons from hydrogen peroxide toxicity. J. Neurosci. 16: 2553-2562.
33. Dorrepaal, C.A., Van Bel, F., Moison, R.M., Shadid, M., Van De Bor, M., Steendijk, P., and Berger, H.M. 1997. Oxidative stress during post hypoxic-ischemia reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition. Pediatr. Res. 41: 321-326.
34. Dringen, R., Gebhardt, R., and Hamprecht, B. 1993. Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res. 623: 208-214.
35. Du, C., Hu, R., Csernansky, C.A., Hsu, C.Y., and Choi, D.W. 1996. Very delayed infarction after mild focal cerebral ischemia: a role for apoptosis? J. Cereb. Blood Flow Metab. 16: 195-201.
36. Dugan, L.L., Sensi, S.L., Canzoniero, L.M., Handran, S.D., Rothman, S.M., Lin, T.S., Goldberg, M.P., and Choi, D.W. 1995. Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. J. Neurosci. 15: 6377-6388.
37. Ekholm, A., Katsura, K., Kristian, T., Liu, M., Folbergrova, J., and Siejso, B.K. 1993. Coupling of cellular energy state and ion homeostasis during recovery following brain ischemia. Brain Res. 604: 185-191.
38. Fabian, R.H., DeWitt, D.S., and Kent, T. A. 1995. In vivo detection of superoxide anion production by the brain using a cytochrome c electrode. J. Cereb. Blood Flow Metab. 15: 242-247.
39. Fedoroff, S., Ahmed, I., Opas, M., and Kalnins, V.I. 1987. Organization of microfilaments in astrocytes that form in the presence of dibutyryl cyclic AMP in cultures, which are similar to reactive astrocytes in vivo. Neuroscience, 22: 255-266.
40. Flamm, E.S., Demopoulos, H.B., Seligman, M.L., Poser, R.G., and Ransohoff, J. 1978. Free radicals in cerebral ischemia. Stroke, 9: 445-447.
41. Furukawa, K., Estus, S., Fu, W., Mark, R.J., and Mattson, M.P. 1997. Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways. J. Cell Biol. 136: 1137-1149.
42. Furuta, A., Price, D.L., Pardo, C.A., Troncoso, J.C., Xu, Z.S., Taniguchi, N., and Martin, L.J. 1995. Localization of superoxide dismutases in Alzheimer's disease and Down's syndrome neocortex and hippocampus. Am. J. Pathol. 146: 357-367.
43. Gale, C.R., Martyn, C.N., Winter, P.D., and Cooper, C. 1995. Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people. Br. Med. J. 310: 1563-1566.
44. Globus, M.Y.-T., Busto, R., Lin, B., Schnippering, H., and Ginsberg, M.D. 1995. Dectection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J. Neurochem. 65: 1250-1256.
45. Goss, J.R., Taffe, K.M., Kochanek, P.M., and DeKosky, S.T. 1997. The antioxidant enzymes glutathione peroxidase and catalase increase following traumatic brain injury in the rat. Exp. Neurol. 146: 291-294.
46. Grünewald, R.A. 1993. Ascorbic acid in the brain. Brain Res. Rev. 18: 123-133.
47. Gwag, B.J., Koh, J.Y., Chen, M.M., Dugan, L.L., Behrens, M.M., Lobner, D., and Choi, D.W. 1995. BDNF or IGF-I potentiates free radical-mediated injury in cortical cell cultures. NeuroReport, 7: 93-96.
48. Hall, E.D. 1995. Inhibition of lipid peroxidation in central nervous system trauma and ischemia. J. Neurol. Sci. 134(Suppl.): 79-83.
49. Hall, E.D. 1996. Efficacy and mechanism of action of the cytoprotective lipid peroxidation inhibitor tirilazad mesylate in subarachnoid haemorrhage. Eur. J. Anaesthesiol. 13: 279-289.
50. Hall, E.D., Andrus, P.K., Smith, S.L., Oostveen, J.A., Scherch, H.M., Lutzke, B.S., Raub, T.J., Sawada, G.A., Palmer, J.R., Banitt, L.S., Tustin, J.S., Belonga, K.L., Ayer, D.E., and Bundy, G.L. 1996. Neuroprotective efficacy of microvascularly-localized versus brain-penetrating antioxidants. Acta Neurochir. 66(Suppl.): 107-113.
51. Halliwell, B. 1995. How to characterize an antioxidant: an update. Biochem. Soc. Symp. 61: 73-101.
52. Halliwell, B. 1996. Vitamin C: antioxidant or pro-oxidant in vivo? Free Radical Res. 25: 439-454.
53. Halsey, J.H., Jr., Conger, K.A., Garcia, J.H., and Sarvary, E. 1991. The contribution of reoxygenation to ischemic brain damage. J. Cereb. Blood Flow Metab. 11: 994-1000.
54. Hammarstrom, L. 1966. Autoradiographic studies on the distribution of 14C-labeled ascorbic acid and dehydroascorbic acid. Acta Physiol. Scand. 70(Suppl. 289): 1-84.
55. Hara, H., Huang, P.L., Panahian, N., Fishman, M.C., and Moskowitz, M.A. 1996. Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occulsion. J. Cereb. Blood Flow Metab. 16: 605-611.
56. +-dependent glutamate uptake in rat hippocampal astrocyte cultures. J. Neurochem. 67: 277-286.
57. Hassel, B., and Sonnewald, U. 1995 Glial formation of pyruvate and lactate from TCA cycle intermediates: implications for the inactivation of transmitter amino acids? J. Neurochem. 65: 2227-2234.
58. Hastings, T.G., Lewis, D. A., and Zigmond, M.J. 1996. Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. Proc. Natl. Acad. Sci. U.S.A. 93: 1956-1961.
59. Heales, S.J., Bolanos, J.P., Land, J.M., and Clark, J.B. 1994. Trolox protects mitochondrial complex IV from nitric oxide-mediated damage in astrocytes. Brain Res. 668: 243-245.
60. Hillered, L., Persson, L., Bolander, H.G., Hallstrom, A., and Ungerstedt, U. 1988. Increased levels of ascorbate in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. Neurosci. Lett. 95: 286-290.
61. Hillered, L., Nilsson, P., Ungerstedt, U., and Ponten, U. 1990. Trauma-induced increase of extracellular ascorbate in rat cerebral cortex. Neurosci. Lett. 113: 328-332.
62. Huang, J., and Philbert, M.A. 1995. Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells. Brain Res. 680: 16-22.
63. Huang, J., and Philbert, M.A. 1996. Cellular responses of cultured cerebral astrocytes to ethacrynic acid-induced perturbation of subcellular glutathione homeostasis. Brain Res. 711: 184-192.
64. + in neuronal cell death during and after anoxia-ischemia. Neurosci. Biobehav. Rev. 21: 129-134.
65. Hussain, S., Slikker, W., Jr., and Ali, S.F. 1995. Age-related changes in antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione in different regions of mouse brain. Int. J. Dev. Neurosci. 13: 811-817.
66. Hussain, S., Slikker, W., Jr., and Ali, S.F. 1996. Role of metallothionein and other antioxidants in scavenging superoxide radicals and their possible role in neuroprotection. Neurochem. Int. 29: 145-152.
67. Ikeda, Y., and Long, D.M. 1990. The molecular basis of brain injury and brain edema: the role of oxygen free radicals. Neurosurgery, 27: 1-11.
68. Juurlink, B.H.J. 1997. Response of glial cells to ischemia: roles of reactive oxygen species and glutathione. Neurosci. Biobehav. Rev. 21: 151-166.
69. Juurlink, B.H.J., Schultke, E., and Hertz, L. 1996. Glutathione release and catabolism during energy substrate reduction in astrocytes. Brain Res. 710: 229-233.
70. Kaltschmidt, B., Uherek, M., Volk, B., Baeuerle, P.A., and Kaltschmidt, C. 1997. Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 94: 2642-2647.
71. Karibe, H., Chen, S.F., Zarow, G.J., Gafni, J., Graham, S.H., Chan, P.H., and Weinstein, P.R. 1994. Mild intraischemic hypothermia suppresses consumption of endogenous antioxidants after temporary focal ischemia in rats. Brain Res. 649: 12-18.
72. Katoh, D., Ikata, T., Katoh, S., Hamada, Y., and Fukuzawa, K. 1996. Effect of dietary vitamin C on compression injury of the spinal cord in a rat mutant unable to synthesize ascorbic acid and its correlation with that of vitamin E. Spinal Cord, 34: 234-238.
73. Kelleher, J.A., Chan, T.Y.Y., Chan, P.H., and Gregory, G.A. 1996. Protection of astrocytes by fructose 1,6-bisphosphate and citrate ameliorates neuronal injury under hypoxic conditions. Brain Res. 726: 167-173.
74. Kim, H., Koehler, R.C., Hum, P.D., Hall, E.D., and Traystman, R.J. 1996. Amelioration of impaired cerebral metabolism after severe acidotic ischemia by tirilazad posttreatment in dogs. Stroke, 27: 114-121.
75. Kimelberg, H.K. 1995. Current concepts of brain edema: review of laboratory investigations. J. Neurosurg. 83: 1051-1059.
76. Kinouchi, H., Epstein, C.J., Mizui, T., Carlson, E., Chen, S.F., and Chan, P.H. 1991. Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 88: 11 158-11 162.
77. Kinuta, Y., Kikuchi, H., Ishikawa, M., Kimura, M., and Itokawa, Y. 1989. Lipid peroxidation in focal cerebral ischemia. J. Neurosurg. 71: 421-429.
78. Klomp, L.W., and Gitlin, J.D. 1996. Expression of the ceruloplasmin gene in the human retina and brain: implications for a pathogenic model in aceruloplasminemia. Human Mol. Genet. 5: 1989-1996.
79. Klomp, L.W., Farhangrazi, Z.S., Dugan, L.L, and Gitlin, J.D. 1996. Ceruloplasmin gene expression in the murine central nervous system. J. Clin. Invest. 98: 207-215.
80. Kondo, T., Reaume, A.G., Huang, T.-T., Carlson, E., Murakami, K., Chen. S.F., Hoffman, E.K., Scott, R.W., Epstein, C.J., and Chan, P.H. 1997. Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J. Neurosci. 17: 4180-4189.
81. Kristian, T., and Siesjo, B.K. 1996. Calcium-related damage in ischemia. Life Sci. 59: 357-367.
82. Kuroda, S., Katsura, K.-I., Tsuchidate, R., and Siesjo, B.K. 1996. Secondary bioenergetic failure after transient focal ischemia is due to mitochondrial injury. Acta Physiol. Scand. 156: 149-150.
83. Landolt, H., Lutz, T.W., Langemann, H., Stauble, D., Mendelowitsch, A., Gratzl, O., and Honegger, C.G. 1992. Extracellular antioxidants and amino acids in the cortex of the rat: monitoring by microdialysis of early ischemic changes. J. Cereb. Blood Flow Metab. 12: 96-102.
84. Largo, C., Cuevas, P., Somjen, G.G., Martin del Rio, R., and Herreras, O. 1996. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival. J. Neurosci. 16: 1219-1229.
85. Lawrence, M.S., Ho, D.Y., Sun, G.H., Steinberg, G.K., and Sapolsky, R.M. 1996a. Overexpression of Bcl-2 with herpes simplex virus vectors protects CNS neurons against neurological insults in vitro and in vivo. J. Neurosci. 16: 486-496.
86. Lawrence, M.S., Sun, G.H., Kunis, D.M., Saydam, T.C., Dash, R., Ho, D.Y., Sapolsky, R.M., and Steinberg, G.K. 1996b. Overexpression of the glucose transporter gene with a herpes simplex viral vector protects striatal neurons against stroke. J. Cereb. Blood Flow Metab. 16: 181-185.
87. Li, P.A., Uchino, H., Elmer, E., and Siesjo, B.K. 1997. Amelioration by cylcosporin A of brain damage following 5 or 10 min of ischemia in rats subjected to preischemic hyperglycemia. Brain Res. 753: 133-140.
88. Linazasoro, G., and Gorospe, A. 1995. Treatment of complicated Parkinson disease with a solution of levodopa and ascorbic acid. Neurologia, 10: 220-223.
89. Liu, X.-H., Kato, H., Nakata, N., Kogure, K., and Kato, K. 1993. An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase in rat hippocampus after transient cerebral ischemia. Brain Res. 625: 29-37.
90. Loeffler, D.A., LeWitt, P.A., Juneau, P.L., Sima, A.A., Nguyen, H.U., DeMaggio, A.J., Brickman, C.M., Brewer, G.J., Dick, R.D., Troyer, M.D., and Kanaley, L. 1996. Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders. Brain Res. 738: 265-274.
91. Longuemare, M.C., Hill, M.P., and Swanson, R.A. 1994. Glycolysis can prevent non-synaptic excitatory amino acid release during hypoxia. NeuroReport, 6: 1789-1792.
92. Lonnrot, K., Metsa-Ketela, T., Molnar, G., Ahonen, J.P., Latvala, M., Peltola, J., Pietila, T., and Alho, H. 1996. The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity. Free Radical Biol. Med. 21: 211-217.
93. Lowndes, H.E., Beiswanger, C.M., Philbert, M.A., and Reuhl, K.R. 1994. Substrates for neural metabolism of xenobiotics in adult and developing brain. Neurotoxicology, 15: 61-73.
94. Lucius, R., and Sievers, J. 1996. Postnatal retinal ganglion cells in vitro: protection against reactive oxygen species (ROS)-induced axonal degeneration by cocultured astrocytes. Brain Res. 743: 56-62.
95. Lundgren, J., Zhang, H., Agardh, C., Smith, M., Evans, P.J., Halliwell, B., and Siesjo, B.K. 1991. Acidosis-induced ischemic brain damage: are free radicals involved? J. Cereb. Blood Flow Metab. 11: 587-596.
96. Lyrer, P., Landolt, H., Kabiersch, A., Langemann, H., and Kaeser, H. 1991. Levels of low molecular weight scavengers in the rat brain during focal ischemia. Brain Res. 567: 317-320.
97. MacGregor, D.G., Higgins, M.J., Jones, P.A., Maxwell, W.O., Watson, M.W., Graham, D.I., and Stone, T.W. 1996. Ascorbate attenuates the systemic kainate-induced neurotoxicity in the rat hippocampus. Brain Res. 727: 133-144.
98. Manganaro, F., Chopra, V.S., Mydlarski, M.B., Bernatchez, G., and Schipper, H.M. 1995. Redox perturbations in cysteamine-stressed astroglia: implications for inclusion formation and gliosis in the aging brain. Free Radical Biol. Med. 19: 823-835.
99. Mark, R.J., Blanc, E.M., and Mattson, M.P. 1996. Amyloid beta-peptide and oxidative cellular injury in Alzheimer's disease. Mol. Neurobiol. 12: 211-224.
100. Mark, R.J., Pang, Z., Geddes, J.W., Uchida, K., and Mattson, M.P. 1997. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J. Neurosci. 17: 1046-1054.
101. Markesbery, W.R. 1997. Oxidative stress hypothesis in Alzheimer's disease. Free Radical Biol. Med. 23: 134-147.
102. Mason, P.A., Dev, B.R., and Freed, C.R. 1995. Ascorbic acid concentration in the lateral hypothalamus is related to plasma osmolality. Brain Res. 37: 305-309.
103. 2+ exchanger in reperfusion-induced delayed cell death of cultured rat astrocytes. Eur. J. Neurosci. 8: 951-958.
104. Matsuo, Y., Kihara, T., Ikeda, M., Ninomiya, M., Onodera, H., and Kogure, K. 1995. Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. J. Cereb. Blood Flow Metab. 15: 941-947.
105. Mattson, M.P., Lovell, M.A., Furukawa, K., and Markesbery, W.R. 1995. Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular calcium concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 65: 1740-1751.
106. May, J.M., Qu, Z.C., and Morrow, J.D. 1996. Interaction of ascorbate and alpha-tocopherol in resealed human erythrocyte ghosts. Transmembrane electron transfer and protection from lipid peroxidation. J. Biol. Chem. 271: 10 577-10 582.
107. McCall, A.L., Van Bueren, A.M., Nipper, V., Moholt-Siebert, M., Downes, H., and Lessov, N. 1996. Forebrain ischemia increases Glut1 protein in brain microvessels and parenchyma. J. Cereb. Blood Flow Metab. 16: 69-76.
108. Megyesi, J.F., and Del Maestro, R.F. 1988. Nuclear magnetic resonance in the investigation of cerebral tumors and cerebral edema: a clue to the cellular alterations that may affect the distribution of water. Biochem. Cell Biol. 66: 1100-1109.
109. Meister, A. 1995. Mitochondrial changes associated with glutathione deficiency. Biochim. Biophys. Acta, 1271: 35-42.
110. Miele, M., Boutelle, M.G., and Fillenz, M. 1994. The physiologically induced release of ascorbate in rat brain is dependent on impulse traffic, calcium influx and glutamate uptake. Neuroscience, 62: 87-91.
111. Mitani, A., Andou, Y., Matsuda, S., Arai, T., Sakanaka, M., and Kataoka, K. 1994. Origin of ischemia-induced glutamate efflux in the CA1 field of the gerbil hippocampus: an in vivo brain microdialysis study. J. Neurochem. 63: 2152-2164.
112. Mizui, T., Kinouchi, H., and Chan, P.H. 1992. Depletion of brain glutathione by buthionine sulfoximine enhances cerebral ischemic injury in rats. Am. J. Physiol. 262: H313-H317.
113. Muizelaar, J.P., Marmarou, A., Young, H.F., Choi, S.C., Wolf, A., Schneider, R., and Kontos, H. 1993. Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol-conjugated superoxide dismutase: a phase II trial. J. Neurosurg. 78: 375-382.
114. Murakami, K., Kondo, T., and Chan, P.H. 1997. Reperfusion following focal cerebal ischemia alters distribution of neuronal cells with DNA fragmentation in mice. Brain Res. 751: 160-164.
115. Myers, K.M., Fiskum, G., Liu, Y., Simmens, S.J., Bredesen, D.E., and Murphy, A.N. 1995. Bcl-2 protects neural cells from cyanide/aglycemic-induced lipid oxidation, mitochondrial injury, and loss of viability. J. Neurochem. 65: 2432-2440.
116. Myllyla, V.V, Heikkinen, E.R., Vapaatalo, H., and Hokkanen, E. 1975. Cyclic AMP concentration and enzyme activity of cerebrospinal fluid in patients with epilepsy or central nervous system damage. Eur. Neurol. 13: 123-130.
117. Nakajima, K., and Suzuki, K. 1995. Immunochemical detection of metallothionein in brain. Neurochem. Int. 27: 73-87.
118. Nakanishi, H., Kawachi, A., Okada, M., Fujiwara, M., and Yamamoto, K. 1996. Protective effect of MK-801 on the anoxia-aglycemia induced damage in the fluorocitrate-treated hippocampal slice of the rat. Brain Res. 732: 232-236.
119. Naus, C.C.G., Bechberger, J.F., Caveney, S., and Wilson, J.X. 1991. Expression of gap junction genes in astrocytes and C6 glioma cells. Neurosci. Lett. 126: 33-36.
120. Neal, J.W., Singhrao, S.K., Jasani, B., and Newman, G.R. 1996. Immunocytochemically detectable metallothionein is expressed by astrocytes in the ischaemic human brain. Neuropathol. Appl. Neurobiol. 22: 243-247.
121. Nelson, C.W., Wei, E.P., Povlishoch, J.T., Kontos, H.A., and Moskowitz, M.A. 1992. Oxygen radicals in cerebral ischemia. Am. J. Physiol. 263: H1356-H1362.
122. O'Connor, E., Devesa, A., Garcia, C., Puertes, I.R., Pellin, A., and Vina, J.R. 1995. Biosynthesis and maintenance of GSH in primary astrocyte cultures: role of L-cystine and ascorbate. Brain Res. 680: 157-163.
123. Ogata, T., Nakamura, Y., Shibata, T., and Kataoka, K. 1992. Release of excitatory amino acids from cultured hippocampal astrocytes induced by hypoxic hypoglycemic stimulation. J. Neurochem. 58: 1957-1959.
124. Oillet, J., Koziel, V., Vert, P., and Daval, J.L. 1996. Influence of post hypoxia reoxygenation conditions on energy metabolism and superoxide production in cultured neurons from the rat forebrain. Pediatr. Res. 39: 598-603.
125. Oka, A., Belliveau, M.J., Rosenberg, P.A., and Volpe, J.J. 1993. Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention. J. Neurosci. 13: 1441-1453.
126. Oppido, P.A., Delfini, R., Innocenzi, G., Di Giugno, G., Pecori-Giraldi, J., Santoro, A., Virno, M., and Cantore, G.P. 1992. Brain oedema and intracranial hypertension treatment by GLIAS. Acta Neurochir. Suppl. 55: 40-42.
127. Oriot, D., Beharry, K., Gordon, J.B., and Aranda, J.V. 1995. Ascorbic acid during cerebral ischemia in newborn piglets. Acta Paediatr. 84: 621-626.
128. Owen, A.D., Schapira, A.H., Jenner, P., and Marsden, C.D. 1996. Oxidative stress and Parkinson's disease. Ann. N.Y. Acad. Sci. 786: 217-223.
129. Panahian, N., Yoshida, T., Huang, P.L., Hedley-Whyte, E.T., Dlakara, T., Fishman, M.C., and Moskowitz, M.A. 1996. Attenuated hippocampal damage after global cerebral ischemia in mice mutant in neuronal nitric oxide synthase. Neuroscience, 72: 343-354.
130. Pantoni, L., Garcia, J.H., and Gutierrez, J.A. 1996. Cerebral white matter is highly vulnerable to ischemia. Stroke, 27: 1641-1646.
131. Patel, M., Day, B.J., Crapo, J.D., Fridovich, I., and McNamara, J.O. 1996. Requirement for superoxide in excitotoxic cell death. Neuron, 16: 345-355.
132. Patterson, J.W., and Mastin, D.W. 1951. Some effects of dehydroascorbic acid on the central nervous system. Am. J. Physiol. 167: 119-126.
133. Pazdernik, T.L., Romanas, M.M., Nelson, S.R., and Samson, F.E. 1994. The effectiveness of ascorbate and urate as antioxidants at concentrations in brain extracellular fluid. FASEB J. 8: A674.
134. Pelletier, O. 1969. Turnover rates of D-isoascorbic acid and L-ascorbic acid in guinea pig organs. Can. J. Physiol. Pharmacol. 47: 993-997.
135. Peuchen, S., Duchen, M.R., and Clark, J.B. 1996. Energy metabolism of adult astrocytes in vitro. Neuroscience, 73: 855-870.
136. Piantadosi, C.A., and Zhang, J. 1996. Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke, 27: 327-331.
137. Prehn, J.H.M., Bindokas, V.P., Jordan, J., Galindo, M.F., Ghadge, G.D., Roos, R.P., Boise, L.H., Thompson, C.B., Krajewski, S., Reed, J.C., and Miller, R.J. 1996. Protective effect of transforming growth factor-beta-1 on beta-amyloid neurotoxicity in rat hippocampal neurons. Mol. Pharmacol. 49: 319-328.
138. Qi, Y., Jamindar, T.M., and Dawson, G. 1995. Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes. J. Neurochem. 64: 2458-2464.
139. Ranjan, A., Theodore, D., Haran, R.P., and Chandy, M.J. 1993. Ascorbic acid and focal cerebral ischaemia in a primate model. Acta Neurochir. 123: 87-91.
140. Rebec, G.V., and Pierce, R.C. 1994. A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission. Prog. Neurobiol. 43: 537-565.
141. Regan, R.F., and Panter, S.S. 1993. Neurotoxicity of hemoglobin in cortical cell culture. Neurosci. Lett. 153: 219-222.
142. Reiter, R.J. 1995. Oxidative processes and antioxidant defense mechanisms in the aging brain. FASEB J. 9: 526-533.
143. Roginsky, V.A., Barsukova, T.K., Bruchelt, G., and Stegmann, H.B. 1997. Iron bound to ferritin catalyzes ascorbate oxidation: effects of chelating agents. Biochim. Biophys. Acta, 1335: 33-39.
144. Romero, I.A., Lister, T., Richards, H.K., Seville, M.P., Wylie, S.P., and Ray, D.E. 1995. Early metabolic changes during m-dinitrobenzene neurotoxicity and the possible role of oxidative stress. Free Radical Biol. Med. 18: 311-319.
145. Rose, R.C. 1993. Cerebral metabolism of oxidized ascorbate. Brain Res. 628: 49-55.
146. Rose, R.C., and Bode, A.M. 1993. Biology of free radical scavengers: an evaluation of ascorbate. FASEB J. 7: 1135-1142.
147. Rose, R.C., Choi, J.-L., and Bode, A.M. 1992. Short term effects of oxidized ascorbic acid on bovine corneal endothelium and human placenta. Life Sci. 50: 1543-1549.
148. Rosenberg, P.A., Amin, S., and Leitner, M. 1992. Glutamate uptake disguises neurotoxic potency of glutamate agonists in cerebral cortex in dissociated cell culture. J. Neurosci. 12: 56-61.
149. Roy, G. 1995. Amino acid current through anion channels in cultured human glial cells. J. Membr. Biol. 147: 35-44.
150. 3H]-D-aspartate from primary astrocyte cultures in response to raised external potassium. J. Neurosci. 16: 7803-7811.
151. Sagara, J., Makino, N., and Bannai, S. 1996. Glutathione efflux from cultured astrocytes. J. Neurochem. 66: 1876-1881.
152. Sano, M., Ernesto, C., Thomas, R.G., Klauber, M.R., Schafer, K., Grundman, M., Woodbury, P., Growdon, J., Cotman, C.W., Pfeiffer, E., Schneider, L.S., and Thai, L.J. 1997. A controlled trial of selegiline, alpha-tocopherol, or both as treatments for Alzheimer's disease. N. Engl. J. Med. 336: 1216-1222.
153. Saris, N.E., and Eriksson, K.O. 1995. Mitochondrial dysfunction in ischaemia-reperfusion. Acta Anaesthesiol. Scand. Suppl. 107: 171-176.
154. Sarnesto, A., Linder, N., and Raivio, K.O. 1996. Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein. Lab. Invest. 74: 48-56.
155. Sato, P.H., and Hall, E.D. 1992. Tirilazad mesylate protects vitamins C and E in brain ischemia-reperfusion injury. J. Neurochem. 58: 2263-2268.
156. Schulz, J.B., Huang, P.L., Matthews, R.T., Passov, D., Fishman, M.C., and Beal, M.F. 1996. Striatal malonate lesions are attenuated in neuronal nitric oxide synthase knockout mice. J. Neurochem. 67: 430-433.
157. Sciamanna, M.A., and Lee, C.P. 1993. Ischemia/reperfusion injury of forebrain mitochondria and protection by ascorbate. Arch. Biochem. Biophys. 305: 215-224.
158. Silver, I. A., and Erecinska, M. 1994. Extracellular glucose concentration in mammalian brain: continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo-, and hyperglycemic animals. J. Neurosci. 14: 5068-5076.
159. Silver, B., Weber, J., and Fisher, M. 1996. Medical therapy for ischemic stroke. Clin. Neuropharmacol. 19: 101-128.
160. Siushansian, R., and Wilson, J.X. 1995. Ascorbate transport and intracellular concentration in cerebral astrocytes. J. Neurochem. 65: 41-49.
161. Siushansian, R., Dixon, S.J., and Wilson, J.X. 1996. Osmotic swelling stimulates ascorbate efflux from cerebral astrocytes. J. Neurochem. 66: 1227-1233.
162. Siushansian, R., Tao, L., Dixon, S.J., and Wilson, J.X. 1997. Cerebral astrocytes transport ascorbic acid and dehydroascorbic acid through distinct mechanisms regulated by cyclic AMP. J. Neurochem. 68: 2378-2385.
163. Smith, D.H., Gennarelli, T.A., and McIntosh, T. 1995. The potential of 21-aminosteroids (lazaroids) as neuroprotective therapies in CNS injuries. CNS Drugs, 3: 159-164.
164. Spencer, J.P., Jenner, P., and Halliwell, B. 1995. Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine. Relevance to Parkinson's disease. NeuroReport, 6: 1480-1484.
165. 51Cr release. Neurochem. Res. 20: 1417-1427.
166. Stanimirovic, D.B., Ball, R., and Durkin, J.P. 1997. Stimulation of glutamate uptake and Na,K-ATPase activity in rat astrocytes exposed to ischemia-like insults. Glia, 19: 123-134.
167. Stone, E.A., and John, S.M. 1992. Stress-induced increase of extracellular levels of cyclic AMP in rat cortex. Brain Res. 597: 144-147.
168. Suyama, K., Saito, K., Chen, G., Pan, B.-S., Manji, H.K., and Potter, W.Z. 1995. Alterations in cyclic AMP generation and G protein subunits following transient ischemia in gerbil hippocampus. J. Cereb. Blood Flow Metab. 15: 877-885.
169. Swanson, R.A., Chen, J., and Graham, S.H. 1994. Glucose can fuel glutamate uptake in ischemic brain. J. Cereb. Blood Flow Metab. 14: 1-6.
170. Swanson, R.A., Liu, J., Miller, J.W., Rothstein, J.D., Farrell, K., Stein, B.A., and Longuemare, M.C. 1997. Neuronal regulation of glutamate transporter subtype expression in astrocytes. J. Neurosci. 17: 932-940.
171. Sweeney, M.I., Yager, J.Y., Walz, W., and Juurlink, B.H.J. 1995. Cellular mechanisms involved in brain ischemia. Can. J. Physiol. Pharmacol. 73: 1525-1535.
172. Takagi, K., Kanemitsu, H., Tomukai, N., Oka, H., Tamura, A., Kohno, M., Mitsuda, K., Yoshika, S., and Sano, K. 1992. Changes of superoxide dismutase activity and ascorbic acid in focal cerebral ischaemia in rats. Neurol. Res. 14: 26-30.
173. Takizawa, S., Matsushima, K., Shinohara, Y., Ogawa, S., Komatsu, N., Utsunomiya, H., and Watanabe, K. 1994. Immunohistochemical localization of glutathione peroxidase in infarcted human brain. J. Neurol. Sci. 122: 66-73.
174. Taylor, B.M., Fleming, W.E., Benjamin, C.W., Wu, Y., Mathews, W.R., and Sun, F.F. 1996. The mechanism of cytoprotective action of lazaroids. I. Inhibition of reactive oxygen species formation and lethal cell injury during periods of energy depletion. J. Pharmacol. Exp. Ther. 276: 1224-1231.
175. The RANTTAS Investigators. 1996. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). Stroke, 27: 1453-1458.
176. Thompson, C.B. 1995. Apoptosis in the pathogenesis and treatment of disease. Science (Washington, D.C.), 267: 1456-1462.
177. Thorburne, S.K., and Juurlink, B.H.J. 1996. Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. J. Neurochem. 67: 1014-1022.
178. Tombaugh, G.C., Yang, S.H., Swanson, R.A., and Sapolsky, R.M. 1992. Glucocorticoids exacerbate hypoxic and hypoglycemic hippocampal injury in vitro: biochemical correlates and a role for astrocytes. J. Neurochem. 59: 137-146.
179. Torp, R., Andine, P., Hagberg, H., Karagulle, T., Blackstad, T.W., and Ottersen, O.P. 1991. Cellular and sub-cellular re-distribution of glutamate-, glutamine-, and taurine-like immunoreactivities during forebrain ischemia: a semiquantitative electron microscope study in rat hippocampus. Neuroscience, 41: 433-447.
180. Tsacopoulos, M., and Magistretti, P.J. 1996. Metabolic coupling between glia and neurons. J. Neurosci. 16: 877-885.
181. Tsai, P.J., Wu, J.P., Lin, N.N., Kuo, J.S., and Yang, C.S. 1996. In vivo, continuous and automatic monitoring of extracellular ascorbic acid by microdialysis and on-line liquid chromatography. J. Chromatogr. B, Biomed. Appl. 686: 151-156.
182. Uemura, Y., Miller, J.M., Matson, W.R., and Beal, M.F. 1991. Neurochemical analysis of focal ischemia in rats. Stroke, 22: 1548-1553.
183. Vapaatalo, H. 1970. Role of cyclic nucleotides in the nervous system. Med. Biol. 52: 200-207.
184. Vatassery, G.T. 1995. In vitro oxidation of vitamins C and E, cholesterol, and thiols in rat brain synaptosomes. Lipids, 30: 1007-1013.
185. Vatassery, G.T. 1996. Oxidation of vitamin E, vitamin C, and thiols in rat brain synaptosomes by peroxynitrite. Biochem. Pharmacol. 52: 579-586.
186. Vatassery, G.T., Smith, W.E., Quach, H.T., and Lai, J.C.K. 1995. In vitro oxidation of vitamin E, vitamin C, thiols and cholesterol in rat brain mitochondria incubated with free radicals. Neurochem. Int. 26: 527-535.
187. Vexler, Z.S., Roberts, T.P.L., Bollen, A.W., Derugin, N., and Arieff, A.I. 1997. Transient cerebral ischemia. Association of apoptosis induction with hypoperfusion. J. Clin. Invest. 99: 1453-1459.
188. Volterra, A., Trotti, D., and Racagni, G. 1994. Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms. Mol. Pharmacol. 46: 986-992.
189. Walker, P.S., Donovan, J.A., Van Ness, B.G., Fellows, R.E., and Pessini, J.E. 1988. Glucose-dependent regulation of glucose transport activity, protein, and mRNA in primary cultures of rat brain glial cells. J. Biol. Chem. 263: 15 594 - 15 601.
190. Wandosell, F., Bovolenta, P., and Nieto-Sampedro, M. 1993. Differences between reactive astrocytes and cultured astrocytes treated with dibutyryl cyclic AMP. J. Neuropathol. Exp. Neurol. 52: 205-215.
191. Wass, C.T., and Lanier, W.L. 1996. Glucose modulation of ischemic brain injury: review and clinical recommendations. Mayo Clin. Proc. 71: 801-812.
192. Waterfall, A.M., Singh, G., Fry, J.R., and Marsden, C.A. 1996. Acute acidosis elevates malondialdehyde in rat brain in vivo. Brain Res. 712: 102-106.
193. Westergaard, N., Sonnewald, U., and Schousboe, A. 1995. Metabolic trafficking between neurons and astrocytes: the glutamate-glutamine cycle revisited. Dev. Neurosci. 17: 203-211.
194. 1-antiproteinase inactivation by ascorbic acid. A comparison with other biological antioxidants. Free Radical Res. 25: 275-283.
195. Wilson, J.X. 1989. Ascorbic acid uptake by a high-affinity sodium-dependent mechanism in cultured rat astrocytes. J. Neurochem. 53: 1064-1071.
196. Wilson, J.X., and Dixon, S.J. 1989. Ascorbic acid transport in mouse and rat astrocytes is reversibly inhibited by furosemide, SITS and DIDS. Neurochem. Res. 14: 1169-1175.
197. Wilson, J.X., and Jaworski, E.M. 1992. Effect of oxygen on ascorbic acid uptake and concentration in embryonic chick brain. Neurochem. Res. 17: 571-576.
198. Wilson, J.X., Jaworski, E.M., and Dixon, S.J. 1991. Evidence for electrogenic sodium-dependent ascorbate transport in rat astroglia. Neurochem. Res. 16: 73-78.
199. Wilson, J.X., Lui, E.M.K., and Del Maestro, R.F. 1992. Developmental profiles of antioxidant enzymes and trace metals in chick embryo. Mech. Ageing Dev. 65: 51-64.
200. Winkler, B.S., De Santis, N., and Solomon, F. 1986. Multiple NADPH-producing pathways control glutathione (GSH) content in retina. Exp. Eye Res. 43: 829-847.
201. Witte, O.W., and Stoll, G. 1997. Delayed and remote effects of focal cortical infarctions: secondary damage and reactive plasticity. Adv. Neurol. 73: 207-227.
202. Yager, J.Y., Kala, G., Hertz, L., and Juurlink, B.H.J. 1994. Correlation between content of high-energy phosphates and hypoxic-ischemic damage in immature and mature astrocytes. Dev. Brain Res. 82: 62-68.
203. Yang, C., Lin, N., Tsai, P., Liu, L., and Kuo, J. 1996. In vivo evidence of hydroxyl radical formation induced by elevation of extracellular glutamate after cerebral ischemia in the cortex of anesthetized rats. Free Radical Biol. Med. 20: 245-250.
204. Yonezawa, M., Black, M.S.A., Gan, X., Rosenberg, P.A., and Volpe, J.J. 1996. Cystine deprivation induces oligodendroglial death: rescue by free radical scavengers and by a diffusible glial factor. J. Neurochem. 67: 566-573.
205. Yoshida, S., Abe, K., Busto, R., Watson, B.D., Kogure, K., and Ginsberg, M.D. 1982. Influence of transient ischemia on lipid-soluble antioxidants, free fatty acids and energy metabolites in rat brain. Brain Res. 245: 307-316.
206. Yu, A.C.H., Gregory, G.A., and Chan, P.H. 1989. Hypoxia-induced dysfunctions and injury of astrocytes in primary cell cultures. J. Cereb. Blood Flow Metab. 8: 20-28.
207. Zaharchuk, G., Hara, H., Huang, P.L., Fishman, M.C., Moskowitz, M.A., Jenkins, B.G., and Rosen, B.R. 1997. Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficent changes in the peri-infarct zone during focal cerebral ischemia. Magn. Reson. Med. 37: 170-175.