1. Lucas, D. and Newhouse, J. (1957) The toxic effects of sodium l-glutamate on the inner layers of the retina. Arch, Ophthalmol. 58, 193-201.

2. Olney, J. W. (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164, 719-721

3. Curtis, D. R., Phillis, J. W., and Watkins, J. (1960) The chemical excitation of spinal neurons by certain acidic amino acids. J. Physiol. (Lond.) 150, 656-682.

4. Crawford, J. M. and Curtis, D. R. (1964) The excitation and depression of mammalian cortical neurons by amino acids. Br. J. Pharm. 23, 323-329.

5. Krnjevic, K. (1974) Chemical nature of synaptic transmission in vertebrates. Physiol. Res. 418, 418-540.

6. Di Chiara, G. and Gessa, G. L. (eds.) (1981), Psychopharmacology Vol. 27 Glutamate as a Neurotransmitter, Advances in Biochemical Raven P, New York.

7. Coyle, J. T. and Schwarcz, R. (1976) Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature 263, 244-246.

8. McGeer, E. G, and McGeer, P. L. (1976) Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids. Nature 263, 517-519.

9. Nadler, J. V., Perry, B. W., and Cotman, C. W. (1978) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271, 676-677.

10. Sloviter, R. S. (1983) "Epileptic" brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies. Brain Res. Bull. 10, 675-697.

11. Rothman, S. (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J. Neu-rosci. 4,1884-1891.

12. Simon, R. P., Swan, J. H., Griffiths, T., and Meldrum, B. S. (1984) Blockade of N-methyl-d-aspartate receptors may protect against ischemic damage in the brain. Science 226, 850-850.

13. Wieloch, T. (1985) Hypoglycemia-induced neuronal damage prevented by an N-methyl-d-aspartate antagonist. Science 230, 681-683.

14. Yoshioka, A., Hardy, M., Younkin, D. P., Grinspan, J. B., Stern, J. L., and Pleasure, D. (1995) Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage. J. Neurochem. 64, 2442-2448.

15. Matute, C., Sanchez-Gomez, M. V., Martinez-Millan, L., and Miledi, R. (1997) Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes. Proc. Natl. Acad. Sci. USA 94, 8830-8835.

16. McDonald, J. W., Althomsons, S. P., Hyrc, K. L., Choi, D. W., and Goldberg, M. P. (1998) Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity. Nat. Med. 4, 291-297.

17. 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.

18. Chen, C. J., Liao, S. L., and Kuo, J. S. (2000) Gliotoxic action of glutamate on cultured astrocytes. J. Neurochem. 75, 1557-1565.

19. Seeburg, P. H. (1993) The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 16, 359-365.

20. Hollmann, M. and Heinemann, S. (1994) Cloned glutamate receptors. Annu. Rev. Neurosci. 17, 31-108.

21. Seeburg, P. H., Higuchi, M., and Sprengel, R. (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res. Rev. 26, 217-229.

22. Nakanishi, S. and Masu, M. (1994) Molecular diversity and functions of glutamate receptors. Annu. Rev. Biophys. Biomol. Struct. 23, 319-348.

23. Conn, P. J. and Pin, J. P. (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol. 37, 205-237.

24. Kerchner, G. A., Kim, A. H., and Choi, D. W., Glutamate-mediated excitotoxicity, Ionotropic Glutamate Receptors in the CNS, In (P. Jonas and H. Monyer, (eds.), Springer-Verlag, Berlin, 1999, pp. 443-469.

25. Nicoletti, F., Bruno, V., Catania, M. V., Battaglia, G., Copani, A., Barbagallo, G., et al. (1999) Group-I metabotropic glutamate receptors: hypotheses to explain their dual role in neurotoxicity and neuroprotection. Neuropharmacology 38, 1477-1484.

26. Cartmell, J. and Schoepp, D. D. (2000) Regulation of neurotransmitter release by metabotropic glutamate receptors. J. Neu-rochem. 75, 889-907.

27. Fagni, L., Chavis, P., Ango, F., and Bockaert, J. (2000) Complex interactions between mGluRs, intracellular Ca2+ stores and ion channels in neurons. Trends Neurosci. 23, 80-88.

28. Choi, D. W. (1988) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 11, 465-469.

29. Olney, J. W., Price, M. T., Samson, L., and Labruyere, J. (1986) The role of specific ions in glutamate neurotoxicity. Neurosci. Lett. 65, 65-71.

30. Turetsky, D. M., Canzoniero, L. M. T., Sensi, S. L., Weiss, J. H., Goldberg, M. P., and Choi, D. W. (1994) Cortical neurones exhibiting kainate-activated Co2+ uptake are selectively vulnerable to AMPA/kainate receptor-mediated toxicity. Neurobiol. Dis. 1, 101-110.

31. Yu, S. P. and Choi, D. W. (1997) Na+-Ca2+ exchange currents in cortical neurons: concomitant forward and reverse operation and effect of glutamate. Eur. J. Neurosci. 9, 1273-1281.

32. Hartley. D. M., Kurth, M. C., Bjerkness, L., Weiss, J. H., and Choi, D. W. (1993) Glutamate receptor-induced 45Ca2+ accumulation in cortical cell culture correlates with subsequent neuronal degeneration. J. Neurosci. 13,1993-2000.

33. Hyrc, K., Handran, S. D., Rothman, S. M., and Goldberg, M. P. (1997) Ionized intracellular calcium concentration predicts excitotoxic neuronal death: observations with low-affinity fluorescent calcium indicators. J. Neurosci. 17, 6669-6677.

34. Grimwood, S., Gilbert, E., Ragan, C. I., and Hutson, P. H. (1996) Modulation of 45Ca2+ influx into cells stably expressing recombinant human NMDA receptors by ligands acting at distinct recognition sites. J. Neurochem. 66, 2589-2595.

35. Grant, E. R., Bacskai, B. J., Pleasure, D. E., Pritchett, D. B., Gallagher, M. J., Kendrick, S. J., et al. (1997) N-Methyl-d-aspartate receptors expressed in a nonneuronal cell line mediate subunit-specific increases in free intracellular calcium. J. Biol. Chem. 272, 647-656.

36. Dugan, L. L., Sensi, S. L., Canzoniero, L. M., Handran, S. D., Rothman, S. M., Lin, T. S., et al. (1995) Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-d-aspartate. J. Neurosci. 15, 6377-6388.

37. Reynolds, I. J. and Hastings, T. G. (1995) Glutamate induces the production of reactive oxygen species in cultured fore-brain neurons following NMDA receptor activation. J. Neurosci. 15, 3318-3327.

38. White, R. J. and Reynolds, I. J. (1995) Mitochondria and Na+/Ca2+ exchange buffer glutamate-induced calcium loads in cultured cortical neurons. J. Neurosci. 15,1318-1328.

39. Schinder, A. F., Olson, E. C., Spitzer, N. C., and Montal, M. (1996) Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J. Neurosci. 16, 6125-6133.

40. White, R. J. and Reynolds. I. J. (1996) Mitochondrial depolarization in glutamate-stimulated neurons: an early signal specific to excitotoxin exposure. J. Neurosci. 16, 5688-5697.

41. Dykens, J. A., Stern, A., and Trenkner, E. (1987) Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. J. Neurochem. 49, 1222-1228.

42. Monyer, H., Hartley, D. M., and Choi, D. W. (1990) 21-Aminosteroids attenuate excitotoxic neuronal injury in cortical cell cultures. Neuron 5, 121-126.

43. Siman, R., Noszek, J. C., and Kegerise, C. (1989) Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage. J. Neurosci. 9, 1579-1590.

44. Lee, K. S., Frank, S., Vanderklish, P., Arai, A., and Lynch, G. (1991) Inhibition of proteolysis protects hippocampal neurons from ischemia. Proc. Natl. Acad. Sci. USA 88, 7233-7237.

45. Brorson, J. R., Manzolillo, P. A., and Miller, R. J. (1994) Ca2+ entry via AMPA/KA receptors and excitotoxicity in cultured cerebellar Purkinje cells. J. Neurosci. 14, 187-197.

46. Dessi, F., Charriaut-Marlangue, C., Khrestchatisky, M., and Ben-Ari, Y. (1993) Glutamate-induced neuronal death is not a programmed cell death in cerebellar culture. J. Neurochem. 60, 1953-1955.

47. Regan, R. F., Panter, S. S., Witz, A., Tilly, J. L., and Giffard, R. G. (1995) Ultrastructure of excitotoxic neuronal death in murine cortical culture. Brain Res. 705, 188-198.

48. Gottron, F. J., Ying, H. S., and Choi, D. W. (1997) Caspase inhibition selectively reduces the apoptotic component of oxygen-glucose deprivation-induced cortical neuronal cell death. Mol. Cell. Neurosci. 9, 159-169.

49. Gwag, B. J., Koh, J. Y., DeMaro, J. A., Ying, H. S., Jacquin, M., and Choi, D. W. (1997) Slowly triggered excitotoxicity occurs by necrosis in cortical cultures. Neuroscience 77, 393-401.

50. Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., et al. (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15, 961-973.

51. Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., and Lipton, S. A. (1995) Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-d-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc. Natl. Acad. Sci. USA 92, 7162-7166.

52. Simonian, N. A., Getz, R. L., Leveque, J. C., Konradi, C., and Coyle, J. T. (1996) Kainate induces apoptosis in neurons. Neuroscience 74, 675-683.

53. Didier, M., Bursztajn, S., Adamec, E., Passani, L., Nixon, R. A., Coyle, J. T., et al. (1996) DNA strand breaks induced by sustained glutamate excitotoxicity in primary neuronal cultures. J. Neurosci. 16, 2238-2250.

54. Dreyer, E. B., Zhang, D., and Lipton, S. A. (1995) Transcriptional or translational inhibition blocks low dose NMDA-medi-ated cell death. Neuroreport 6, 942-944.

55. Finiels, F., Robert, J. J., Samolyk, M. L., Privat, A., Mallet, J., and Revah, F. (1995) Induction of neuronal apoptosis by excitotoxins associated with long-lasting increase of 12-O-tetradecanoylphorbol 13-acetate-responsive element-binding activity. J. Neurochem. 65, 1027-1034.

56. Tenneti, L., D'Emilia, D. M., Troy, C. M., and Lipton, S. A. (1998) Role of caspases in N-methyl-d-aspartate-induced apoptosis in cerebrocortical neurons. J. Neurochem. 71, 946-959.

57. Xiang, H., Kinoshita, Y., Knudson, C. M., Korsmeyer, S. J., Schwartzkroin, P. A., and Morrison, R. S. (1998) Bax involvement in p53-mediated neuronal cell death. J. Neurosci. 18,1363-1373.

58. McDonald, J. W., Behrens, M. I., Chung, C., Bhattacharyya, T., and Choi, D. W. (1997) Susceptibility to apoptosis is enhanced in immature cortical neurons. Brain Res. 759, 228-232.

59. Frederickson, C. J. (1989) Neurobiology of zinc and zinc-containing neurons. Int. Rev. Neurobiol. 31, 145-238.

60. Lee, J. M., Zipfel, G. J., and Choi, D. W. (1999) The changing landscape of ischaemic brain injury mechanisms. Nature 399, A7-A14.

61. Weiss, J. H., Sensi, S. L., and Koh, J. Y. (2000) Zn2+: a novel ionic mediator of neural injury in brain disease. Trends Pharmacol. Sci. 21, 395-401.

62. Peters, S., Koh, J.-Y., and Choi, D. W. (1987) Zinc selectively blocks the action of N-methyl-d-aspartate on cortical neurons. Science 236, 589-593.

63. Westbrook, G. L. and Mayer, M. L. (1987) Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 328, 640-643.

64. Christine, C. W. and Choi, D. W. (1988) Zinc alters NMDA receptor-mediated channel events on cortical neurons. Neurology 38 (Suppl), 274-275.

65. Smart, T. G., Xie, X., and Krishek, B. J. (1994) Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc. Prog. Neurobiol. 42, 393-441.

66. Manzerra, P., Behrens, M. I., Canzoniero, L. M., Wang. X. Q., Heidinger, V., Ichinose, T., et al. (2001) Zinc induces a Src family kinase-mediated upregulation of NMDA receptor activity and excitotoxicit. Proc. Natl. Acad. Sci. USA 98, 11051-11061.

67. Choi, D. W. and Koh, J. Y. (1998) Zinc and brain injury. Annu. Rev. Neurosci. 21, 347-375.

68. Tonder, N., Johansen, F. F., Frederickson, C. J., Zimmer, J., and Diemer, N. H. (1990) Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat. Neurosci. Lett. 109, 247-252.

69. Koh, J.-Y., Suh, S. W., Gwag, B. J., He, Y. Y., Hsu, C. Y., and Choi, D. W. (1996) The role of zinc in selective neuronal death after transient global cerebral ischemia. Science 272, 1013-1016.

70. Frederickson, C. J., Hernandez, M. D., Goik, S. A., Morton, J. D., and McGinty. J. F. (1988) Loss of zinc staining from hip-pocampal mossy fibers during kainic acid induced seizures: a histofluorescence study. Brain Res. 446, 383-386.

71. Frederickson. C. J., Hernandez, M. D., and McGinty, J. F. (1989) Translocation of zinc may contribute to seizure-induced death of neurons. Brain Res. 480, 317-321.

72. Yu. S. P., Yeh, C. H., Sensi, S. L., Gwag, B. J., Canzoniero, L. M., Farhangrazi, Z. S., et al. (1997) Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 278, 114-117.

73. Yu, S. P., Farhangrazi, Z. S., Ying, H. S., Yeh, C. H., and Choi, D. W. (1998) Enhancement of outward potassium current may participate in beta-amyloid peptide-induced cortical neuronal death. Neurobiol. Dis. 5, 81-88.

74. Yu, S. P., Yeh, C., Strasser, U., Tian, M., and Choi, D. W. (1999) NMDA receptor-mediated K+ efflux and neuronal apopto-sis. Science 284, 336-339.

75. Choi, D. W., Yu, S. P., Wei, L., and Gottron, F. (1998) Potassium channel blockers attenuate neuronal deaths induced by hypoxic insults in cortical culture and transient focal ischemia in the rat. Soc. Neurosci. Abst. 24, 1226.

76. Huang, H., Gao, T. M., Gong, L. W., Zhuang, Z. Y., and Li, X. M. (2001) Potassium channel blocker TEA prevents CA1 hippocampal injury following transient forebrain ischemia in adult rats. Neurosci. Lett. 305, 83-86.

77. Goldberg, M. P., Weiss., J. H., Pham, P. C., and Choi, D. W. (1987) N-Methyl-d-aspartate receptors mediate hypoxic neuronal injury in cortical culture. J. Pharmacol. Exp. Ther. 243, 784-791.

78. Kaku, D. A., Goldberg, M. P., and Choi, D. W. (1991) Antagonism of non-NMDA receptors augments the neuroprotective effect of NMDA receptor blockade in cortical cultures subjected to prolonged deprivation of oxygen and glucose. Brain Res. 554, 344-347.

79. Storgaard, J., Kornblit, B. T., Zimmer, J., and Gramsbergen, J. B. (2000) 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate. Exp. Neurol. 164, 227-235.

80. Goldberg, M. P. and Choi, D. W. (1990) Intracellular free calcium increases in cultured cortical neurons deprived of oxygen and glucose. Stroke 21, III75-III7.

81. Goldberg, M. P. and Choi, D. W. (1993) Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury. J. Neurosci. 13, 3510-3524.

82. Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N. H. (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neu-rochem. 43, 1369-1374.

83. Meldrum, B. S. (1994) The role of glutamate in epilepsy and other CNS disorders. Neurology 44, S14-S23.

84. Katayama, Y., Becker, D. P., Tamura, T., and Hovda, D. A. (1990) Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg. 73, 889-900.

85. Buchan, A. M., Lesiuk, H., Barnes, K. A., Li, H., Huang, Z. G., Smith, K. E., et al. (1993) AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists? Stroke 24, I148-I152.

86. Sheardown, M. J., Nielsen, E. O., Hansen, A. J., Jacobsen, P., and Honore, T. (1990) 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. Science 247, 571-574.

87. Diemer, N. H., Jorgensen, M. B., Johansen, F. F., Sheardown, M., and Honore, T. (1992) Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX. Acta Neurol. Scand. 86, 45-49.

88. Nellgard, B. and Wieloch, T. (1992) Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in the rat brain following transient severe cerebral ischemia. J. Cereb, Blood Flow Metab. 12, 2-11.

89. Buchan, A. M., Xue, D., Huang, Z. G., Smith, K. H., and Lesiuk, H. (1991) Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia. Neuroreport 2, 473-476.

90. Gill, R., Nordholm, L., and Lodge, D. (1992) The neuroprotective actions of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) in a rat focal ischaemia model. Brain Res. 580, 35-43.

91. Gotti, B., Duverger, D., Bertin, J., Carter, C., Dupont, R., Frost, J., et al. (1988) Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia. J. Pharmacol. Exp. Ther. 247,1211-1221.

92. Ozyurt, E., Graham, D. I., Woodruff, G. N., and McCulloch, J. (1988) Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat. J. Cereb. Blood Flow Metab. 8, 138-143.

93. Park, C. K., Nehls, D. G., Graham, D. I., Teasdale, G. M., and McCulloch, J. (1988) The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann. Neurol. 24, 543-551.

94. Hayes. R. L., Jenkins, L. W., Lyeth, B. G., Balster, R. L., Robinson, S. E., Clifton, G. L., et al. (1988) Pretreatment with phencyclidine, an N-methyl-d-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. J. Neurotrauma 5, 259-274.

95. Faden, A. I., Demediuk, P., Panter, S. S., and Vink, R. (1989) The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244, 798-800.

96. Wrathall, J. R., Teng, Y. D., Choiniere, D., and Mundt, D. J. (1992) Evidence that local non-NMDA receptors contribute to functional deficits in contusive spinal cord injury. Brain Res. 586, 140-143.

97. Novelli, A., Reilly, J. A., Lysko. P. G., and Henneberry, R. C. (1988) Glutamate becomes neurotoxic via the N-methyl-d-aspartate receptor when intracellular energy levels are reduced. Brain Res. 451, 205-212.

98. Beal, M. F. (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 23, 298-304.

99. Nicholls, D. G., and Ward, M. W. (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts. Trends Neurosci. 23, 166-174.

100. Ward, M. W., Rego, A. C., Frenguelli, B. G., and Nicholls, D. G. (2000) Mitochondrial membrane potential and glutamate excitotoxicity in cultured cerebellar granule cells. J. Neurosci. 20, 7208-7219.

101. Sun, Y., Savanenin, A., Reddy, P. H., and Liu, Y. F. (2001) Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-d-aspartate receptors via post-synaptic density 95. J. Biol. Chem. 276, 24,713-24,718.

102. Greenamyre, J. T. (1991) Neuronal bioenergetic defects, excitotoxicity and Alzheimer's disease: "use it and lose it". Neuro-biol. Aging 12, 334-336; discussion 352-355.

103 Harkany, T., Abraham. I., Konya, C., Nyakas, C., Zarandi, M., Penke, B., et al. (2000) Mechanisms of beta-amyloid neurotoxicity: perspectives of pharmacotherapy.Rev. Neurosci. 11, 329-382.

104. Dickie, B. G., Holmes, C., and Greenfield, S. A. (1996) Neurotoxic and neurotrophic effects of chronic N-methyl-d-aspar-tate exposure upon mesencephalic dopaminergic neurons in organotypic culture. Neuroscience 72, 731-741.

105. Beal, M. F. (1998) Excitotoxicity and nitric oxide in Parkinson's disease pathogenesis. Ann. Neurol. 44, S110-S114.

106. Rothstein, J. D., Martin, L. J., and Kuncl, R. W. (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N. Engl. J. Med. 326,1464-1468.

107. Ferrer, I., Martin, F., Serrano, T., Reiriz, J., Perez-Navarro, E., Alberch, J., et al. (1995) Both apoptosis and necrosis occur following intrastriatal administration of excitotoxins. Acta Neuropathol. 90, 504-510.

108. Portera-Cailliau, C., Hedreen, J. C., Price, D. L., and Koliatsos, V. E. (1995) Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J. Neurosci. 15, 3775-3787.

109. Qin, Z. H., Wang, Y., and Chase, T. N. (1996) Stimulation of N-methyl-d-aspartate receptors induces apoptosis in rat brain. Brain Res. 725, 166-176.

110. Portera-Cailliau, C., Price, D. L., and Martin, L. J. (1997) Excitotoxic neuronal death in the immature brain is an apopto-sis-necrosis morphological continuum. J. Comp. Neurol. 378, 70-87.

111. Kirino, T. (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239, 57-69.

112. Pulsinelli, W. A., Brierley, J. B., and Plum, F. (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann. Neurol. 11, 491-498.

113. Zeng, Y. S. and Xu, Z. C. (2000) Co-existence of necrosis and apoptosis in rat hippocampus following transient forebrain ischemia. Neurosci. Res. 37, 113-125.

114. Lipton, P. (1999) Ischemic cell death in brain neurons. Physiol. Rev. 79, 1431-1568.

115. Kitagawa, K., Matsumoto, M., Tsujimoto, Y., Ohtsuki, T., Kuwabara, K., Matsushita, K., et al. (1998) Amelioration of hippocampal neuronal damage after global ischemia by neuronal overexpression of BCL-2 in transgenic mice. Stroke 29, 2616-2621.

116. Gillardon, F., Kiprianova, I., Sandkuhler, J., Hossmann, K.-A., and Spranger, M. (1999) Inhibition of caspases prevents cell death of hippocampal CA1 neurons, but not impairment of hippocampal long-term potentiation following global ischemia. Neuroscience 93, 1219-1222.

117. 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.

118. Endres, M., Wang, Z. Q., Namura, S., Waeber, C., and Moskowitz, M. A. (1997) Ischemic brain injury is mediated by the activation of poly(ADP- ribose)polymerase. J. Cereb. Blood Flow Metab. 17,1143-1151.

119. Fink, K., Zhu, J., Namura, S., Shimizu-Sasamata, M., Endres, M., Ma, J., et al. (1998) Prolonged therapeutic window for ischemic brain damage caused by delayed caspase activation. J. Cereb. Blood Flow Metab. 18, 1071-1076.

120. Snider, B. J., Du, C., Wei, L., and Choi, D. W. (2001) Cycloheximide reduces infarct volume when administered up to six hours after mild focal ischemia in rats. Brain Res. 917,147-157.

121. Rink, A., Fung, K. M., Trojanowski, J. Q., Lee, V. M., Neugebauer, E., and McIntosh, T. K. (1995) Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am. J. Pathol. 147, 1575-1583.

122. Crowe, M. J., Bresnahan, J. C., Shuman, S. L., Masters, J. N., and Beattie, M. S. (1997) Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat. Med. 3, 73-76.

123. Liu, X. Z., Xu, X. M., Hu, R., Du, C., Zhang, S. X., McDonald, J. W., et al. (1997) Neuronal and glial apoptosis after traumatic spinal cord injury. J. Neurosci. 17, 5395-5406.

124. Yong, C., Arnold, P. M., Zoubine, M. N., Citron, B. A., Watanabe, I., Berman, N. E., et al. (1998) Apoptosis in cellular compartments of rat spinal cord after severe contusion injury. J. Neurotrauma 15, 459-472.

125. Lassmann, H., Bancher, C., Breitschopf, H., Wegiel, J., Bobinski, M., Jellinger, K., et al. (1995) Cell death in Alzheimer's disease evaluated by DNA fragmentation in situ. Acta Neuropathol. (Berl.) 89, 35-41.

126. Smale, G., Nichols, N. R., Brady, D. R., Finch, C. E., and Horton, W. E., Jr. (1995) Evidence for apoptotic cell death in Alzheimer's disease. Exp. Neurol. 133, 225-230.

127. Anderson, A. J., Su, J. H., and Cotman, C. W. (1996) DNA damage and apoptosis in Alzheimer's disease: colocaliza-tion with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay. J. Neurosci. 16, 1710-1719.

128. Johnson, E. M., Jr., Koike, T., and Franklin, J. (1992) A "calcium set-point hypothesis" of neuronal dependence on neurotrophic factor. Exp. Neurol. 115, 163-166.

129. Koike, T., Martin, D. P., and Johnson, E. M., Jr. (1989) Role of Ca2+ channels in the ability of membrane depolarization to prevent neuronal death induced by trophic-factor deprivation: evidence that levels of internal Ca2+ determine nerve growth factor dependence of sympathetic ganglion cells. Proc. Natl. Acad, Sci. USA 86, 6421-6425.

130. Koike, T. and Tanaka, S. (1991) Evidence that nerve growth factor dependence of sympathetic neurons for survival in vitro may be determined by levels of cytoplasmic free Ca2+. Proc. Natl. Acad. Sci. USA 88, 3892-3896.

131. Lasher, R. S. and Zagon, I. S. (1972) The effect of potassium on neuronal differentiation in cultures of dissociated newborn rat cerebellum. Brain Res. 41, 482-488.

132. Pearson, H., Graham, M. E., and Burgoyne, R. D. (1992) Relationship between intracellular free calcium concentration and NMDA-induced cerebellar granule cell survival in vitro. Eur. J. Neurosci. 4, 1369-1375.

133. Galli, C., Meucci, O., Scorziello, A., Werge, T. M., Calissano, P., and Schettini, G. (1995) Apoptosis in cerebellar granule cells is blocked by high KC1, forskolin, and IGF-1 through distinct mechanisms of action: the involvement of intracellular calcium and RNA synthesis. J. Neurosci. 15, 1172-1179.

134. Gallo, V., Kingsbury, A., Balazs, R., and J0rgensen, O. S. (1987) The role of depolarization in the survival and differentiation of cerebellar granule cells in culture. J. Neurosci. 7, 2203-2213.

135. Yan, G.-M., Ni, B., Weller, M., Wood, K. A., and Paul, S. M. (1994) Depolarization or glutamate receptor activation blocks apoptotic cell death of cultured cerebellar granule neurons. Brain Res. 656, 43-51.

136. Levick, V., Coffey, H., and D'Mello, S. R. (1995) Opposing effects of thapsigargin on the survival of developing cerebellar granule neurons in culture. Brain Res. 676, 325-335.

137. Babcock, D. J., Gottron, F. J., and Choi, D. W. (1999) Raising intracellular calcium attenuates ischemic apoptosis in vitro. Soc. Neurosci. Abst. 25, 2103.

138. Terro, F., Esclaire, F., Yardin, C., and Hugon, J. (2000) N-methyl-d-aspartate receptor blockade enhances neuronal apoptosis induced by serum deprivation. Neurosci. Lett. 278, 149-152.

139. Bansal, N., Houle, A. G., and Melnykovych, G. (1990) Dexamethasone-induced killing of neoplastic cells of lymphoid derivation: lack of early calcium involvement. J. Cell. Physiol. 143, 105-109.

140. Baffy, G., Miyashita, T., Williamson, J. R., and Reed, J. C. (1993) Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J. Biol. Chem. 268, 6511-6519.

141. Kluck, R. M., McDougall, C. A., Harmon, B. V., and Haliday, J. W. (1994) Calcium chelators induce apoptosis—evidence that raised intracellular ionised calcium is not essential for apoptosis. Biochim. Biophys. Acta 1223, 247-254.

142. Zhu, W.-H. and Loh, T.-T. (1995) Roles of calcium in the regulation of apoptosis in HL-60 promyelocytic leukemia cells. Life Sci. 57, 2091-2099.

143. Chiesa, R., Angeretti, N., Del Bo, R., Lucca, E., Munna, E., and Forloni, G. (1998) Extracellular calcium deprivation in astrocytes: regulation of mRNA expression and apoptosis. J. Neurochem. 70,1474-1483.

144. Lam, M., Dubyak, G., and Distelhorst, C. W. (1993) Effect of glucocorticosteroid treatment on intracellular calcium home-ostasis in mouse lymphoma cells. Mol. Endocrinol. 7, 686-693.

145. Bian, X., Hughes, F. M., Jr., Huang, Y., Cidlowski, J. A., and Putney, J. W., Jr. (1997) Roles of cytoplasmic Ca2+ and intracellular Ca2+ stores in induction and suppression of apoptosis in S49 cells. Am. J. Physiol. 272, C1241-C1249.

146. Bennett, M. R. and Huxlin, K. R. (1996) Neuronal cell death in the mammalian nervous system: the calmortin hypothesis. Gen Pharmacol. 27, 407-419.

147. McConkey, D. J. and Orrenius, S. (1997) The role of calcium in the regulation of apoptosis. Biochem. Biophys. Res. Commun. 239, 357-366.

148. Distelhorst, C. W. and Dubyak, G. (1998) Role of calcium in glucocorticosteroid-induced apoptosis of thymocytes and lymphoma cells: resurrection of old theories by new findings. Blood 91, 731-734.

149. Toescu, E. C. (1998) Apoptosis and cell death in neuronal cells: where does Ca2+ fit in? Cell Calcium 24, 387-403.

150. Yu, S. P. and Choi, D. W. (2000) Ions, cell volume, and apoptosis. Proc. Natl. Acad. Sci. USA 97, 9360-9362.

151. Olney, J. W., Labruyere, J., and Price, M. T. (1989) Pathological changes induced in cerebrocortical neurons by phencycli-dine and related drugs. Science 244, 1360-1362.

152. Onley, J. W., Labruyere, J., Wang, G., Wozniak, D. F., Price, M. T., and Sesma, M. A. (1991) NMDA antagonist neurotoxicity: mechanism and prevention. Science 254, 1515-1518.

153. Sharp, F. R., Butman, M., Koistinaho, J., Aardalen, K., Nakki, R., Massa, S. M., et al. (1994) Phencyclidine induction of the hsp 70 stress gene in injured pyramidal neurons is mediated via multiple receptors and voltage gated calcium channels. Neuroscience 62,1079-1092.

154. Hwang, J. Y., Kim, Y. H., Ahn, Y. H., Wie, M. B., and Koh, J. Y. (1999) N-Methyl-d-aspartate receptor blockade induces neuronal apoptosis in cortical culture. Exp. Neurol. 159, 124-130.

155. Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vockler, J., Dikranian, K., et al. (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283, 70-74.

156. Ikonomidou, C., Bittigau, P., Ishimaru, M. J., Wozniak, D. F., Koch, C., Genz, K., et al. (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287,1056-1060.

157. Phol, D., Bittigau, P., Ishimaru, M. J., Stadthaus, D., Hubner, C., Onley, J. W., et al. (1999) N-methyl-d-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain. Proc. Natl. Acad. Sci. USA 96, 2508-2573.

158. Davis, S. M., Lees, K. R., Albers, G. W., Diener, H. C., Markabi, S., Karlsson, G. et al. (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31, 347-354.

159 Kieburtz, K., Feigin, A., McDermott, M., Como, P., Abwender, D., Zimmerman, C., et al. (1996) A controlled trial of remacemide hydrochloride in Huntington's disease. Mov. Cement Disord. 11, 273-277.

160. Murman, D. L., Giordani, B., Mellow, A. M., Johanns, J. R., Little, R. J. A., Hariharan, M., et al. (1997) Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease. Neurology 49, 153-161.

161. Snider, B. J., Tee, L. Y., Canzoniero, L. M., and Choi, D. W. (2002) NMDA antagonists exacerbate neuronal death caused by proteasome inhibition in cultured cortical and striatal neurons. Eur. J. Neurosci. 15, 419-428.

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