Molecular pathways in cerebral ischemia: Cues to novel therapeutic strategies

Molecular Neurobiology

Volumn 27, Issue 1, 2003, Pages 33-72

  Onténiente, Brigitte ^a   Rasika, Sowmyalakshmí ^a   Benchoua, Alexandra ^a   Guégan, Christelle ^a  

^a FACULTÉ DE MÉDECINE   (France)

Author keywords

Apoptosis; Caspases; Clinical research; Stroke; Therapy

Indexed keywords

3 (5 CHLORO 2 METHOXYPHENYL) 3 FLUORO 2,3 DIHYDRO 6 TRIFLUOROMETHYL 1H INDOL 2 ONE; 3,3 BIS(3 FLUOROPHENYL) N METHYLPROPYLAMINE; 4 PHOSPHONOMETHYLPIPECOLIC ACID; 6 (1 IMIDAZOLYL) 7 NITRO 2,3 QUINOXALINEDIONE; 6 NITRO 7 SULFAMOYLBENZO[F]QUINOXALINE 2,3 DIONE; 6,7 DICHLORO 5 NITRO 2,3 QUINOXALINEDIONE; APTIGANEL; BAY 3702; CEREBRIX; CLOMETHIAZOLE; DECAHYDRO 6 [2 (1H TETRAZOL 5 YL)ETHYL] 3 ISOQUINOLINECARBOXYLIC ACID; DIZOCILPINE; EBSELEN; ELIPRODIL; ETHYLENEGLYCOL 1,2 BIS(2 AMINOPHENYL) ETHER N,N,N',N' TETRAACETIC ACID BIS(2 OCTYLOXYETHYL) ESTER; FLUNARIZINE; FOSPHENYTOIN SODIUM; GAVESTINEL; GYK 52466; LUBELUZOLE; MEMANTINE; NEUROPROTECTIVE AGENT; NIMODIPINE; RECOMBINANT BASIC FIBROBLAST GROWTH FACTOR; REMACEMIDE; REPINOTAN; RILUZOLE; TIRILAZAD; UNCLASSIFIED DRUG; UNINDEXED DRUG; [1,2,3,4 TETRAHYDRO 7 (1H IMIDAZOL 1 YL) 6 NITRO 2,3 DIOXO 1 QUINOXALINYL]ACETIC ACID; [[3,4 DIHYDRO 7 MORPHOLINO 2,3 DIOXO 6 (TRIFLUOROMETHYL) 1(2H) QUINOXALINYL]METHYL]PHOSPHONIC ACID;

AGITATION; APOPTOSIS; ARTICLE; BRAIN ISCHEMIA; CATATONIA; CELL FUNCTION; CELL TRANSPLANTATION; CLINICAL TRIAL; DEATH; DELIRIUM; DISABILITY; DISEASE SEVERITY; DRUG ACTIVITY; DRUG MECHANISM; DRUG MEGADOSE; HALLUCINATION; HUMAN; INDUSTRIALIZATION; NERVE CELL DEGENERATION; NEUROPROTECTION; NONHUMAN; PARANOIA; RISK FACTOR; SEDATION; SIDE EFFECT; STROKE; TRANSPLANTATION;

EID: 17344384728     PISSN: 08937648     EISSN: None     Source Type: Journal    
DOI: 10.1385/MN:27:1:33     Document Type: Article

References (369)

1. Wardlaw J. M., Dennis M. S., Lindley R. I., Sellar R. J., and Warlow C. P. (1996) The validity of a simple clinical classification of acute ischaemic stroke. J. Neurol. 243, 274-279.
2. Allan W. C. (1990) The IVH complex of lesions: cerebrovascular injury in the preterm infant. Neurol Clin. 8, 529-551.
3. Davenport R. and Dennis M. (2000) Neurological emergencies: acute stroke. J. Neurol. Neurosurg. Psychiatry 68, 277-288.
4. Furlan A., Higashida R., Wechsler L., Gent M., Rowley H., Kase C., et al. (1999) Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism JAMA 282, 2003-2011.
5. Conference T. a. b. o. t. i. h. h. (1992), in National Health and Welfare, pp. 12-23, NINDS Publ., Victoria.
6. Garcia J. H., Liu K. F., and Ho K. L. (1995) Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26, 636-642, discussion 643.
7. Lipton P. (1999) Ischemic cell death in brain neurons. Physiol. Rev. 79, 1431-1568.
8. Linnik M. D., Zobrist R. H., and Hatfield M. D. (1993) Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 24, 2002-2008, discussion 2008-2009.
9. Charriaut-Marlangue C., Margaill I., Represa A., Popovici T., Plotkine M., and Ben-Ari Y. (1996) Apoptosis and necrosis after reversible focal ischemia: an in situ DNA fragmentation analysis. J. Cereb Blood Flow Metab. 16, 186-194.
10. Guégan C., Ceballos-Picot I., Nicole A., Kato H., Onténiente B., and Sola B. (1998) Recruitment of several neuroprotective pathways after permanent focal ischemia in mice. Exp. Neurol. 154, 371-380.
11. Clarke C. J., Hales A., Hunt A., and Foxwell B. M. (1998) IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity. Eur. J. Immunol. 28, 1719-1726.
12. 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.
13. Wyllie A. H., Kerr J. F., and Currie A. R. (1980) Cell death: the significance of apoptosis. Int. Rev. Cytol. 68, 251-306.
14. Colbourne F., Sutherland G. R., and Auer R. N. (1999) Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia. J. Neurosci. 19, 4200-4210.
15. Portera-Cailliau C., Price D. L., and Martin L. J. (1997) Non-NMDA and NMDA receptor-mediated excitotoxic neuronal deaths in adult brain are morphologically distinct: further evidence for an apoptosis-necrosis continuum. J. Comp. Neurol. 378, 88-104.
16. Martin L. J., Al-Abdulla N. A., Brambrink A. M., Kirsch J. R., Sieber F. E., and Portera-Cailliau C. (1998) Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: a perspective on the contributions of apoptosis and necrosis. Brain Res. Bull. 46, 281-309.
17. Choi D. W. and Gage F. H. (1996) Disease, transplantation and regeneration. Curr. Opin. Neurobiol. 6, 635-637.
18. Gwag B. J., Lobner D., Koh J. Y., Wie M. B., and Choi D. W. (1995) Blockade of glutamate receptors unmasks neuronal apoptosis after oxygen-glucose deprivation in vitro. Neuroscience 68, 615-619.
19. Leist M., Single B., Castoldi A. F., Kuhnle S., and Nicotera P. (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J. Exp. Med. 185, 1481-1486.
20. Melino G., Catani M. V., Corazzari M., Guerrieri P., and Bernassola F. (2000) Nitric oxide can inhibit apoptosis or switch it into necrosis. Cell Mol. Life Sci. 57, 612-622.
21. Lemasters J. J., Qian T., Bradham C. A., Brenner D. A., Cascio W. E., Trost L. C., et al. (1999) Mitochondrial dysfunction in the pathogenesis of necrotic and apoptotic cell death. J. Bioenerg. Biomembr. 31, 305-319.
22. Hata R., Mies G., Wiessner C., Fritze K., Hesselbarth D., Brinker G., et al. (1998) A reproducible model of middle cerebral artery occlusion in mice: hemodynamic, biochemical, and magnetic resonance imaging. J. Cereb. Blood Flow Metab 18, 367-375.
23. Johnson D. E. (2000) Programmed cell death regulation: basic mechanisms and therapeutic opportunities. Leukemia 14, 1340-1344.
24. Martin R. L., Lloyd H. G., and Cowan A. I. (1994) The early events of oxygen and glucose deprivation: setting the scene for neuronal death? Trends Neurosci. 17, 251-257.
25. Sun G. Y. and Foudin L. L. (1984) On the status of lysolecithin in rat cerebral cortex during ischemia. J. Neurochem. 43, 1081-1086.
26. Graham S. H., Chen J., Lan J., Leach M. J., and Simon R. P. (1994) Neuroprotective effects of a use-dependent blocker of voltage-dependent sodium channels, BW619C89, in rat middle cerebral artery occlusion. J. Pharmacol. Exp. Ther. 269, 854-859.
27. Smith S. E. and Meldrum B. S. (1995) Cerebro-protective effect of lamotrigine after focal ischemia in rats. Stroke 26, 117-121; discussion 121-122.
28. Fujitani T., Adachi N., Miyazaki H., Liu K., Nakamura Y., Kataoka K., et al. (1994) Lidocaine protects hippocampal neurons against ischemic damage by preventing increase of extracellular excitatory amino acids: a microdialysis study in Mongolian gerbils. Neurosci. Lett. 179, 91-94.
29. Lysko P. G., Webb C. L., Yue T. L., Gu J. L., and Feuerstein G. (1994) Neuroprotective effects of tetrodotoxin as a Na+ channel modulator and glutamate release inhibitor in cultured rat cerebellar neurons and in gerbil global brain ischemia. Stroke 25, 2476-2482.
30. Crumrine R. C., Bergstrand K., Cooper A. T., Faison W. L., and Cooper B. R. (1997) Lamotrigine protects hippocampal CA1 neurons from ischemic damage after cardiac arrest. Stroke 28, 2230-2236; discussion 2237.
31. Lekieffre D. and Meldrum B. S. (1993) The pyrimidine-derivative, BW1003C87, protects CA1 and striatal neurons following transient severe forebrain ischaemia in rats. A microdialysis and histological study. Neuroscience 56, 93-99.
32. Rataud J., Debarnot F., Mary V., Pratt J., and Stutzmann J. M. (1994) Comparative study of voltage-sensitive sodium channel blockers in focal ischaemia and electric convulsions in rodents. Neurosci Lett. 172, 19-23.
33. Diener H. C., Cortens M., Ford G., Grotta J., Hacke W., Kaste M., et al. (2000) Lubeluzole in acute ischemic stroke treatment: a double-blind study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebo. Stroke 31, 2543-2451.
34. 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, 850-852.
35. 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. Neurochem. 43, 1369-1374.
36. Shimada N., Graf R., Rosner G., Wakayama A., George C. P., and Heiss W. D. (1989) Ischemic flow threshold for extracellular glutamate increase in cat cortex. J. Cereb. Blood Flow Metab. 9, 603-606.
37. Baker C. J., Fiore A. J., Frazzini V. I., Choudhri T. F., Zubay G. P., and Solomon R. A. (1995) Intraischemic hypothermia decreases the release of glutmate in the cores of permanent focal cerebral infarcts. Neurosurgery 36, 994-1001; discussion 1001-1002.
38. Obrenovitch T. P., Urenjak J., Richards D. A., Ueda Y., Curzon G., and Symon L. (1993) Extracellular neuroactive amino acids in the rat striatum during ischaemia: comparison between penumbral conditions and ischaemia with sustained anoxic depolarisation. J. Neurochem. 61, 178-186.
39. Rossi D. J., Oshima T., and Attwell D. (2002) Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403, 316-321.
40. 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.
41. Choi D. W. and Rothman S. M. (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu. Rev. Neurosci. 13, 171-182.
42. Olney J. W. (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164, 719-721.
43. 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.
44. Buchan A. and Pulsinelli W. A. (1990) Hypothermia but not the N-methyl-D-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J. Neurosci. 10, 311-316.
45. Hoffman C. A. and Boast C. A. (1995) Neuroprotection by MK-801 in temperature maintained gerbils. Brain Res. Bull. 38, 405-409.
46. 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.
47. Uematsu D., Araki N., Greenberg J. H., Sladky J., and Reivich M. (1991) Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage. Neurology 41, 88-94.
48. Gill R., Hargreaves R. J., and Kemp J. A. (1995) The neuroprotective effect of the glycine site antagonist 3R-(+)-cis-4-methyl-HA966 (L-687,414) in a rat model of focal ischaemia. J. Cereb. Blood Flow Metab. 15, 197-204.
49. Bullock R., Graham D. I., Chen M. H., Lowe D., and McCulloch J. (1990) Focal cerebral ischemia in the cat: pretreatment with a competitive NMDA receptor antagonist, D-CPP-ene. J. Cereb. Blood Flow Metab. 10, 668-674.
50. Sauer D., Weber E., Luond G., Da Silva F., and Allegrini P. R. (1995) The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats. J. Cereb. Blood Flow Metab. 15, 602-610.
51. Lang-Lazdunski L., Heurteaux C., Vaillant N., Widmann C., and Lazdunski M. (1999) Riluzole prevents ischemic spinal cord injury caused by aortic crossclamping. J. Thorac. Cardiovasc. Surg. 117, 881-889.
52. Andine P., Orwar O., Jacobson I., Sandberg M., and Hagberg H. (1991) Changes in extracellular amino acids and spontaneous neuronal activity during ischemia and extended reflow in the CA1 of the rat hippocampus. J. Neurochem. 57, 222-229.
53. Matsumoto K., Lo E. H., Pierce A. R., Halpern E. F., and Newcomb R. (1996) Secondary elevation of extracellular neurotransmitter amino acids in the reperfusion phase following focal cerebral ischemia. J. Cereb. Blood Flow Metab. 16, 114-124.
54. Yao H., Markgraf C. G., Dietrich W. D., Prado R., Watson B. D., and Ginsberg M. D. (1994) Glutamate antagonist MK-801 attenuates incomplete but not complete infarction in thrombotic distal middle cerebral artery occlusion in Wistar rats. Brain Res. 642, 117-122.
55. Nakamura K., Hatakeyama T., Furuta S., and Sakaki S. (1993) The role of early Ca2+ influx in the pathogenesis of delayed neuronal death after brief forebrain ischemia in gerbils. Brain Res. 613, 181-192.
56. Perkins W. J., Lanier W. L., Karlsson B. R., Milde J. H., and Michenfelder J. D. (1989) The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia. Brain Res. 498, 34-44.
57. Takizawa S., Hogan M., and Hakim A. M. (1991) The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia. J. Cereb. Blood Flow Metab. 11, 786-793.
58. Robertson S. C., Wetjen N. M., Beer B. J., and Loftus C. M. (1997) Pre- and postischemic effects of the NMDA receptor antagonist dizocilpine maleate (MK-801) on collateral cerebral blood flow. J. Neurosurg. 87, 927-933.
59. Morikawa E., Mori H., Kiyama Y., Mishina M., Asano T., and Kirino T. (1998) Attenuation of focal ischemic brain injury in mice deficient in the epsilon 1 (NR2A) subunit of NMDA receptor. J. Neurosci. 18, 9727-9732.
60. Buchan A. M., Li H., Cho S., and Pulsinelli W. A. (1991) Blockade of the AMPA receptor prevents CA1 hippocampal injury following severe but transient forebrain ischemia in adult rats. Neurosci Lett. 132, 255-258.
61. Li H. and Buchan A. M. (1993) Treatment with an AMPA antagonist 12 hours following severe normothermic forebrain ischemia prevents CA1 neuronal injury. J. Cereb. Blood Flow Metab. 13, 933-939.
62. Lobner D. and Lipton P. (1993) Intracellular calcium levels and calcium fluxes in the CA1 region of the rat hippocampal slice during in vitro ischemia: relationship to electrophysiological cell damage. J. Neurosci. 13, 4861-4871.
63. Zhang Y. and Lipton P. (1999) Cytosolic Ca2+ changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na+-dependent Ca2+ release from mitochondria. J. Neurosci. 19, 3307-3315.
64. Davis M. and Barer D. (1999) Neuroprotection in acute ischaemic stroke. II: Clinical potential. Vasc. Med. 4, 149-163.
65. Seif el Nasr M., Peruche B., Rossberg C., Mennel H. D., and Krieglstein J. (1990) Neuroprotective effect of memantine demonstrated in vivo and in vitro. Eur. J. Pharmacol. 185, 19-24.
66. Mies G., Kohno K. and Hossmann K. A. (1994) Prevention of periinfarct direct current shifts with glutamate antagonist NBQX following occlusion of the middle cerebral artery in the rat. J. Cereb. Blood Flow Metab. 14, 802-807.
67. Ben-Ari Y. and Khrestchatisky M. (1998) The GluR2 (GluRB) hypothesis in ischemia: missing links. Trends Neurosci. 21, 241-242.
68. Pellegrini-Giampietro D. E., Gorter J. A., Bennett M. V., and Zukin R.S. (1997) The GluR2 (GluR-B) hypothesis: Ca(2+)-permeable AMPA receptors in neurological disorders [see comments]. Trends Neurosci. 20, 464-470.
69. Hollmann M., Hartley M., and Heinemann S. (1991) Ca2+ permeability of KA-AMPA - gated glutamate receptor channels depends on subunit composition. Science 252, 851-853.
70. Pollard H., Heron A., Moreau J., Ben-Ari Y., and Khrestchatisky M. (1993) Alterations of the GluR-B AMPA receptor subunit flip/flop expression in kainate-induced epilepsy and ischemia. Neuroscience 57, 545-554.
71. Heurteaux C., Lauritzen I., Widmann C., and Lazdunski M. (1995) Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc. Natl. Acad. Sci. USA 92, 4666-4670.
72. Kohler M., Burnashev N., Sakmann B., and Seeburg P. H. (1993) Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron 10, 491-500.
73. Bullock R., Graham D. I., Swanson S., and McCulloch J. (1994) Neuroprotective effect of the AMPA receptor antagonist LY-293558 in focal cerebral ischemia in the cat. J. Cereb. Blood Flow Metab. 14, 466-471.
74. Yatsugi S., Takahashi M., Kawasaki-Yatsugi S., Koshiya K., Sakamoto S., Uematsu D., et al. (1996) Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats. J. Cereb. Blood Flow Metab. 16, 959-966.
75. Shimizu-Sasamata M., Kano T., Rogowska J., Wolf G. L., Moskowitz M. A., and Lo E. H. (1998) YM872, a highly water-soluble AMPA receptor antagonist, preserves the hemodynamic penumbra and reduces brain injury after permanent focal ischemia in rats. Stroke 29, 2141-2148.
76. Turski L., Huth A., Sheardown M., McDonald F., Neuhaus R., Schneider H. H., et al. (1998) ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proc. Natl. Acad. Sci. USA 95, 10,960-10,965.
77. 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.
78. Ankarcrona M., Dypbukt J. M., Orrenius S., and Nicotera P. (1996) Calcineurin and mitochondrial function in glutamate-induced neuronal cell death. FEBS Lett. 394, 321-324.
79. Budd S. L. and Nicholls D. G. (1996) Mitochondria, calcium regulation, and acute glutamate excitotoxicity in cultured cerebellar granule cells. J. Neurochem. 67, 2282-2291.
80. Buisson A. and Choi D. W. (1995) The inhibitory mGluR agonist, S-4-carboxy-3-hydroxy-phenylglycine selectively attenuates NMDA neurotoxicity and oxygen-glucose deprivation-induced neuronal death. Neuropharmacology 34, 1081-1087.
81. Chiamulera C., Costa S., and Reggiani A. (1990) Effect of NMDA- and strychnine-insensitive glycine site antagonists on NMDA-mediated convulsions and learning. Psychopharmacology 102, 551-552.
82. Henrich-Noack P., Hatton C. D., and Reymann K. G. (1998) The mGlu receptor ligand (S)-4C3HPG protects neurons after global ischaemia in gerbils. Neuroreport 9, 985-988.
83. Pizzi M., Fallacara C., Arrighi V., Memo M., and Spano P. F. (1993) Attenuation of excitatory amino acid toxicity by metabotropic glutamate receptor agonists and aniracetam in primary cultures of cerebellar granule cells. J. Neurochem. 61, 683-689.
84. Kristián T. and Siesjö B. K. (1996) Calcium-related damage in ischemia. Life Sci. 59, 357-367.
85. Blaustein M. P. and Golovina V. A. (2001) Structural complexity and functional diversity of endoplasmic reticulum Ca(2+) stores. Trends Neurosci. 24, 602-608.
86. Scarpa A. and Azzone G. F. (1970) The mechanism of ion translocation in mitochondria. 4. Coupling of K+ efflux with Ca2+ uptake. Eur. J. Biochem. 12, 328-335.
87. Kass I. S. and Lipton P. (1986) Calcium and long-term transmission damage following anoxia in dentate gyrus and CA1 regions of the rat hippocampal slice. J. Physiol. 378, 313-334.
88. Harris R. J., Symon L., Branston N. M., and Bayhan M. (1981) Changes in extracellular calcium activity in cerebral ischaemia. J. Cereb. Blood Flow Metab. 1, 203-209.
89. Kristián T., Gido G., Kuroda S., Schutz A., and Siesjö B. K. (1998) Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion. Exp. Brain Res. 120, 503-509.
90. Andine P., Jacobson I., and Hagberg H. (1992) Enhanced calcium uptake by CA1 pyramidal cell dendrites in the postischemic phase despite subnormal evoked field potentials: excitatory amino acid receptor dependency and relationship to neuronal damage. J. Cereb. Blood Flow Metab. 12, 773-783.
91. Ohta S., Furuta S., Matsubara I., Kohno K., Kumon Y., and Sakaki S. (1996) Calcium movement in ischemia-tolerant hippocampal CA1 neurons after transient forebrain ischemia in gerbils. J. Cereb. Blood Flow Metab. 16, 915-922.
92. DeGraba T. J., Ostrow P. T., and Grotta J. C. (1993) Threshold of calcium disturbances after focal cerebral ischemia in rats. Implications of the window of therapeutic opportunity. Stroke 24, 1212-1216; discussion 1216-1217.
93. Meyer F. B. (1990) Calcium antagonists and vasospasm. Neurosurg. Clin. N. Am. 1, 367-376.
94. Deshpande J. K. and Wieloch T. (1986) Flunarizine, a calcium entry blocker, ameliorates ischemic brain damage in the rat. Anesthesiology 64, 215-224.
95. Mossakowski M. J. and Gadamski R. (1990) Nimodipine prevents delayed neuronal death of sector CA1 pyramidal cells in short-term forebrain ischemia in Mongolian gerbils. Stroke 21, IV120-122.
96. Nuglisch J., Karkoutly C., Mennel H. D. Rossberg C., and Krieglstein J. (1990) Protective effect of nimodipine against ischemic neuronal damage in rat hippocampus without changing postischemic cerebral blood flow. J. Cereb. Blood Flow Metab. 10, 654-659.
97. Uematsu D., Greenberg J. H., Hickey W. F., and Reivich M. (1989) Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats. Stroke 20, 1531-1537.
98. Valentino K., Newcomb R., Gadbois T., Singh T., Bowersox S., Bitner S., et al. (1993) A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia. Proc. Natl. Acad. Sci. USA 90, 7894-7897.
99. Buchan A. M., Gertler S. Z., Li H., Xue D., Huang Z. G., Chaundy K. E., et al. (1994) A selective N-type Ca(2+)-channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia. J. Cereb. Blood Flow Metab. 14, 903-910.
100. Takizawa S., Matsushima K., Fujita H., Nanri K., Ogawa S., and Shinohara Y. (1995) A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia. J. Cereb. Blood Flow Metab. 15, 611-618.
101. Horn J., de Haan R. J., Vermeulen M., and Limburg M. (2001) Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial. Stroke 32, 461-465.
102. Franke C. L., Palm R., Dalby M., Schoonderwaldt H. C., Hantson L., Eriksson B., et al. (1996) Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands. Acta Neurol. Scand. 93, 56-60.
103. Mohr J., Orgogozo J., Harrison M., Hermerici M., Wahlgren N., Gelmers J., et al. (1994) Meta-analysis of oral nimodipine trials in acute ischemic stroke. Cerebrovasc. Dis. 4, 177-210.
104. Mitchell P. (1961) Nature 191, 144-148.
105. Morin D., Hauet T., Spedding M., and Tillement J. (2001) Mitochondria as target for anti-ischemic drugs. Adv. Drug Deliv. Rev. 49, 151-174.
106. Haworth R. A. and Hunter D. R. (1979) The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch. Biochem. Biophys. 195, 460-467.
107. Skulachev V. P. (1996) Why are mitochondria involved in apoptosis? Permeability transition pores and apoptosis as selective mechanisms to eliminate superoxide-producing mitochondria and cell. FEBS Lett. 397, 7-10.
108. Petit P. X., Susin S. A., Zamzami N., Mignotte B., and Kroemer G. (1996) Mitochondria and programmed cell death: back to the future. FEBS Lett. 396, 7-13.
109. Zoratti M. and Szabo I. (1995) The mitochondrial permeability transition. Biochim. Biophys. Acta 1241, 139-176.
110. Wolf A., Trendelenburg C. F., Diez-Fernandez C., Prieto P., Houy S., Trommer W. E., et al. (1997) Cyclosporine A-induced oxidative stress in rat hepatocytes. J. Pharmacol. Exp. Ther. 280, 1328-1334.
111. Liu X., Kim C. N., Yang J., Jemmerson R., and Wang X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157.
112. Susin S. A., Zamzami N., Castedo M., Hirsch T., Marchetti P., Macho A., et al. (1996) Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J. Exp. Med. 184, 1331-1341.
113. Lorenzo H. K., Susin S. A., Penninger J., and Kroemer G. (1999) Apoptosis inducing factor (AIF): a phylogenetically old, caspase- independent effector of cell death. Cell Death Differ. 6, 516-524.
114. Desagher S. and Martinou J. C. (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol. 10, 369-377.
115. Morin D., Papadopoulos V., and Tillement J.-P. (2002) Prevention of cell damage in ischaemia: novel molecular targets in mitochondria. Expt. Opin. Ther. Targets 6, 315-334.
116. Love S. (1999) Oxidative stress in brain ischemia. Brain Pathol. 9, 119-131.
117. Siesjö B. K., Elmer E., Janelidze S., Keep M., Kristian T., Ouyang Y. B., et al. (1999) Role and mechanisms of secondary mitochondrial failure. Acta Neurochir. Suppl. 73, 7-13.
118. Marshall J. W., Duffin K. J., Green A. R., and Ridley R. M. (2001) NXY-059, a free radical - trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in a primate species. Stroke 32, 190-198.
119. Spinnewyn B., Blavet N., and Clostre F. (1986) [Effects of Ginkgo biloba extract on a cerebral ischemia model in gerbils]. Presse Med. 15, 1511-1515.
120. Clark W. M., Rinker L. G., Lessov N. S., Lowery S. L., and Cipolla M. J. (2001) Efficacy of antioxidant therapies in transient focal ischemia in mice. Stroke 32, 1000-1004.
121. Yamaguchi T., Sano K., Takakura K., Saito I., Shinohara Y., Asano T., et al. (1998) Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke 29, 12-17.
122. Cuzzocrea S., Riley D. P., Caputi A. P., and Salvemini D. (2001) Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol. Rev. 53, 135-139.
123. Chabrier P. E., Auguet M., Spinnewyn B., Auvin S., Cornet S., Dermerle-Pallardy C., et al. (1999) BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: a promising neuroprotective strategy. Proc. Natl. Acad. Sci. USA 96, 10,824-10,829.
124. Baker K., Marcus C. B., Huffman K., Kruk H., Malfroy B., and Doctrow S. R. (1998) Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury. J. Pharmacol. Exp. Ther. 284, 215-221.
125. Cai J. and Jones D. P. (1998) Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss. J. Biol. Chem. 273, 11,401-11,404.
126. Madesh M. and Hajnoczky G. (2001) VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J. Cell. Biol. 155, 1003-1015.
127. Li P., Nijhawan D., Budihardjo I., Srinivasula S. M., Ahmad M., Alnemri E. S., et al. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.
128. Zhivotovsky B., Burgess D. H., Schlegel J., Porn M. I., Vanags D., and Orrenius S. (1997) Proteases in Fas-mediated apoptosis. J. Cell Biochem. 64, 43-49.
129. Krippner A., Matsuno-Yagi A., Gottlieb R. A., and Babior B. M. (1996) Loss of function of cytochrome c in Jurkat cells undergoing fas-mediated apoptosis. J. Biol. Chem. 271, 21,629-21,636.
130. Stefanelli C., Bonavita F., Stanic I., Farruggia G., Falcieri E., Robuffo I., et al. (1997) ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis. Biochem. J. 322, 909-917.
131. Li F., Srinivasan A., Wang Y., Armstrong R. C., Tomaselli K. J., and Fritz L. C. (1997) Cell-specific induction of apoptosis by microinjection of cytochrome c. Bcl-xL has activity independent of cytochrome c release. J. Biol. Chem. 272, 30,299-30,305.
132. Gross A., McDonnell J. M., and Korsmeyer S. J. (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-1911.
133. Green D. R., and Reed J. C. (1998) Mitochondria and apoptosis. Science 281, 1309-1312.
134. Jurgensmeier J. M., Xie Z., Deveraux Q., Ellerby L., Bredesen D., and Reed J. C. (1998) Bax directly induces release of cytochrome c from isolated mitochondria. Proc. Natl. Acad. Sci. USA 95, 4997-5002.
135. Vander Heiden M. G., Chandel N. S., Williamson E. K., Schumacker P. T., and Thompson C. B. (1997) Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria [see comments]. Cell 91, 627-637.
136. Kluck R. M., Bossy-Wetzel E., Green D. R., and Newmeyer D. D. (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132-1136.
137. Hockenbery D. M., Oltvai Z. N., Yin X. M., Milliman C. L., and Korsmeyer S. J. (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75, 241-251.
138. Kane D. J., Sarafian T. A., Anton R., Hahn H., Gralla E. B., Valentine J. S., et al. (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274-1277.
139. Chen D. F., Schneider G. E., Martinou J. C., and Tonegawa S. (1997) Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 385, 434-439.
140. Chinnaiyan A. M., O'Rourke K., Tewari M., and Dixit V. M. (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81, 505-512.
141. Seshagiri S. and Miller L. K. (1997) Caenorhabditis elegans CED-4 stimulates CED-3 processing and CED-3-induced apoptosis. Curr. Biol. 7, 455-460.
142. Pettmann B. and Henderson C. E. (1998) Neuronal cell death. Neuron 20, 633-647.
143. Antonawich F. J., Federoff H. J., and Davis J. N. (1999) BCL-2 transduction, using a herpes simplex virus amplicon, protects hippocampal neurons from transient global ischemia. Exp. Neurol. 156, 130-137.
144. Wiessner C., Allegrini P. R., Rupalla K., Sauer D., Oltersdorf T., McGregor A. L., et al. (1999) Neuron-specific transgene expression of Bcl-XL but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice. Neurosci. Lett. 268, 119-122.
145. Yah C., Chen J., Chen D., Minami M., Pei W., Yin X. M., et al. (2000) Overexpression of the cell death suppressor Bcl-w in ischemic brain: implications for a neuroprotective role via the mitochondrial pathway. J. Cereb. Blood Flow Metab. 20, 620-630.
146. Hata R., Gillardon F., Michaelidis T. M., and Hossmarm K. A. (1999) Targeted disruption of the bcl-2 gene in mice exacerbates focal ischemic brain injury. Metab. Brain Dis. 14, 117-124.
147. Chen J., Simon R. P., Nagayama T., Zhu R., Loeffert J. E., Watkins S. C., et al. (2000) Suppression of endogenous bcl-2 expression by antisense treatment exacerbates ischemic neuronal death. J. Cereb. Blood Flow Metab. 20, 1033-1039.
148. Martinou J. C., Dubois-Dauphin M., Staple J. K., Rodriguez I., Frankowski H., Missotten M., et al. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017-1030.
149. Krajewski S., Mai J. K., Krajewska M., Sikorska M., Mossakowski M. J., and Reed J. C. (1995) Upregulation of bax protein levels in neurons following cerebral ischemia. J. Neurosci. 15, 6364-6376.
150. Gillardon F., Lenz C., Waschke K. F., Krajewski S., Reed J. C., Zimmermann M., et al. (1996) Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats. Brain Res. Mol. Brain Res. 40, 254-260.
151. Isenmann S., Stoll G., Schroeter M., Krajewski S., Reed J. C., and Bahr M. (1998) Differential regulation of Bax, Bcl-2, and Bcl-X proteins in focal cortical ischemia in the rat. Brain Pathol. 8, 49-62; discussion 62-63.
152. Wolter K. G., Hsu Y. T., Smith C. L., Nechushtan A., Xi X. G., and Youle R. J. (1997) Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139, 1281-1292.
153. Degterev A., Boyce M., and Yuan J. (2001) The channel of death. J. Cell Biol. 155, 695-696.
154. Cao G., Minami M., Pei W., Yan C., Chen D., O'Horo C., et al. (2001) Intracellular Bax translocation after transient cerebral ischemia: implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death. J. Cereb. Blood Flow Metab. 21, 321-333.
155. Plesnila N., Zinkel S., Le D. A., Amin-Hanjani S., Wu Y., Qiu J., et al. (2001) BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia. Proc. Natl. Acad. Sci. USA 98, 15,318-15,323.
156. Alnemri E. S., Livingston D. J., Nicholson D. W., Salvesen G., Thornberry N. A., Wong W. W., et al. (1996) Human ICE/CED-3 protease nomenclature [letter]. Cell 87, 171.
157. Nicholson D. W. and Thornberry N. A. (1997) Caspases: killer proteases. Trends Biochem. Sci. 22, 299-306.
158. Wolf C. M. and Eastman A. (1999) The temporal relationship between protein phosphatase, mitochondrial cytochrome c release, and caspase activation in apoptosis. Exp. Cell Res. 247, 505-513.
159. Nicholson D. W. (1999) Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6, 1028-1042.
160. Nunez G., Benedict M. A., Hu Y., and Inohara N. (1998) Caspases: the proteases of the apoptotic pathway. Oncogene 17, 3237-3245.
161. Earnshaw W. C., Martins L. M., and Kaufmann S. H. (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochem. 68, 383-424.
162. Zhivotovsky B., Samali A., Gahm A., and Orrenius S. (1999) Caspases: their intracellular localization and translocation during apoptosis. Cell Death Differ. 6, 644-651.
163. Cryns V. and Yuan J. (1998) Proteases to die for. Genes Dev. 12, 1551-1570.
164. Thornberry N. A. and Lazebnik Y. (1998) Caspases: enemies within. Science 281, 1312-1316.
165. Slee E. A., Adrain C., and Martin S. J. (1999) Serial killers: ordering caspase activation events in apoptosis. Cell Death Differ. 6, 1067-1074.
166. Brockstedt E., Rickers A., Kostka S., Laubersheimer A., Dorken B., Wittmann-Liebold B., et al. (1998) Identification of apoptosis-associated proteins in a human Burkitt lymphoma cell line. Cleavage of heterogeneous nuclear ribonucleoprotein A1 by caspase 3. J. Biol. Chem. 273, 28,057-28,064.
167. Schwartz L. M. and Milligan C. E. (1996) Cold thoughts of death: the role of ICE proteases in neuronal cell death. Trends Neurosci. 19, 555-562.
168. Villa P., Kaufmann S. H., and Earnshaw W. C. (1997) Caspases and caspase inhibitors. Trends Biochem Sci. 22, 388-393.
169. Rami A., Agarwal R., Botez G., and Winckler J. (2000) mu-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage. Brain Res. 866, 299-312.
170. Loddick S. A., MacKenzie A., and Rothwell N. J. (1996) An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat. Neuroreport 7, 1465-1468.
171. Hara H., Friedlander R. M., Gagliardini V., Ayata C., Fink K., Huang Z., et al. (1997) Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc. Natl. Acad. Sci. USA 94, 2007-2012.
172. Wiessner C., Sauer D., Alaimo D., and Allegrini P. R. (2000) Protective effect of a caspase inhibitor in models for cerebral ischemia in vitro and in vivo. Cell Mol. Biol. (Noisy-le-grand). 46, 53-62.
173. Friedlander R. M., Gagliardini V., Hara H., Fink K. B., Li W., MacDonald G., et al. (1997) Expression of a dominant negative mutant of interleukin-1 beta converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury. J. Exp. Med. 185, 933-940.
174. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B. A., et al. (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403, 98-103.
175. Susin S. A., Lorenzo H. K., Zamzami N., Marzo I., Brenner C., Larochette N., et al. (1999) Mitochondrial release of caspase-2 and -9 during the apoptotic process. J. Exp. Med. 189, 381-394.
176. Zou H., Henzel W. J., Liu X., Lutschg A., and Wang X. (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 [see comments]. Cell 90, 405-413.
177. Fortin A., Cregan S. P., MacLaurin J. G., Kushwaha N., Hickman E. S., Thompson C. S., et al. (2001) APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death. J. Cell Biol. 155, 207-216.
178. Hofmann K., Bucher P., and Tschopp J. (1997) The CARD domain: a new apoptotic signalling motif. Trends Biochem. Sci. 22, 155-156.
179. Fujita E., Urase K., Egashira J., Miho Y., Isahara K., Uchiyama Y., et al. (2000) Detection of caspase-9 activation in the cell death of the Bcl-x-deficient mouse embryo nervous system by cleavage sites-directed antisera. Brain Res. Dev. Brain Res. 122, 135-147.
180. Susin S. A., Zamzami N., Castedo M., Daugas E., Wang H. G., Geley S., et al. (1997) The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis. J. Exp. Med. 186, 25-37.
181. Marzo I., Susin S. A., Petit P. X., Ravagnan L., Brenner C., Larochette N., et al. (1998) Caspases disrupt mitochondrial membrane barrier function. FEBS Lett. 427, 198-202.
182. Green D. and Kroemer G. (1998) The central executioners of apoptosis: caspases or mitochondria? Trends Cell Biol. 8, 267-271.
183. Krajewski S., Krajewska M., Ellerby L. M., Welsh K., Xie Z., Deveraux Q. L., et al. (1999) Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia. Proc. Natl. Acad. Sci. USA 96, 5752-5757.
184. Noshita N., Sugawara T., Fujimura M., Morita-Fujimura Y., and Chan P. H. (2001) Manganese superoxide dismutase affects cytochrome c release and caspase-9 activation after transient focal cerebral ischemia in mice. J. Cereb. Blood Flow Metab. 21, 557-567.
185. Guégan C. and Sola B. (2000) Early and sequential recruitment of apoptotic effectors after focal permanent ischemia in mice. Brain Res. 856, 93-100.
186. Benchoua A., Guegan C., Couriaud C., Hosseini H., Sampaio N., Morin D., et al. (2001) Specific caspase pathways are activated in the two stages of cerebral infarction. J. Neurosci. 21, 7127-7134.
187. Genini D., Budihardjo I., Plunkett W., Wang X., Carrera C. J., Cottam H. B., et al. (2000) Nucleotide requirements for the in vitro activation of the apoptosis protein-activating factor-1-mediated caspase pathway. J. Biol. Chem. 275, 29-34.
188. Dubois-Dauphin M., Pfister Y., Vallet P.G., and Savioz A. (2001) Prevention of apoptotic neuronal death by controlling procaspases? A point of view. Brain Res. Brain Res. Rev. 36, 196-203.
189. Schneider P. and Tschopp J. (2000) Apoptosis induced by death receptors. Pharm. Acta Helv. 74, 281-286.
190. Ashkenazi A. and Dixit V. M. (1998) Death receptors: signaling and modulation. Science 281, 1305-1308.
191. Mariani S. M., Matiba B., Armandola E. A., and Krammer P. H. (1997) Interleukin 1 beta-converting enzyme related proteases/caspases are involved in TRAIL-induced apoptosis of myeloma and leukemia cells. J. Cell Biol. 137, 221-229.
192. Kischkel F. C., Hellbardt S., Behrmann I., Germer M., Pawlita M., Krammer P. H., et al. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14, 5579-5588.
193. Fernandes-Alnemri T., Armstrong R. C., Krebs J., Srinivasula S. M., Wang L., Bullrich F., et al. (1996) In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc. Natl. Acad. Sci. USA 93, 7464-7469.
194. Medema J. P., Scaffidi C., Kischkel F. C., Shevchenko A., Mann M., Krammer P. H., et al. (1997) FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 16, 2794-2804.
195. Muzio M., Stockwell B. R., Stennicke H. R., Salvesen G. S., and Dixit V. M. (1998) An induced proximity model for caspase-8 activation. J. Biol. Chem. 273, 2926-2930.
196. Nagata S. (1997) Apoptosis by death factor. Cell 88, 355-365.
197. Hsu H., Xiong J., and Goeddel D. V. (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81, 495-504.
198. Wang J., Chun H. J., Wong W., Spencer D. M., and Lenardo M. J. (2001) Caspase-10 is an initiator caspase in death receptor signaling. Proc. Natl. Acad. Sci. USA 98, 13,884-13,888.
199. Kischkel F. C., Lawrence D. A., Tinel A., LeBlanc H., Virmani A., Schow P., et al. (2001) Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J. Biol. Chem. 276, 46,639-46,646.
200. Stennicke H. R., Jurgensmeier J. M., Shin H., Deveraux Q., Wolf B. B., Yang X., et al. (1998) Pro-caspase-3 is a major physiologic target of caspase-8. J. Biol. Chem. 273, 27,084-27,090.
201. Harrison D. C., Roberts J., Campbell C. A., Crook B., Davis R., Deen K., et al. (2000) TR3 death receptor expression in the normal and ischaemic brain. Neuroscience 96, 147-160.
202. Jin K., Graham S. H., Mao X., Nagayama T., Simon R. P., and Greenberg D. A. (2001) Fas (CD95) may mediate delayed cell death in hippocampal CA1 sector after global cerebral ischemia. J. Cereb. Blood Flow Metab. 21, 1411-1421.
203. Buttini M., Appel K., Sauter A., Gebicke-Haerter P. J., and Boddeke H. W. (1996) Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience 71, 1-16.
204. Martin-Villalba A., Herr I., Jeremias I., Hahne M., Brandt R., Vogel J., et al. (1999) CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. J. Neurosci. 19, 3809-3817.
205. Martin-Villalba A., Hahne M., Kleber S., Vogel J., Falk W., Schenkel J., et al. (2001) Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke. Cell Death Differ. 8, 679-686.
206. Herdegen T., Claret F. X., Kallunki T., Martin-Villalba A., Winter C., Hunter T., et al. (1998) Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal kinases after neuronal injury. J. Neurosci. 18, 5124-5135.
207. Lukaszevicz A.-C., Sampaïo N., Guégan C., Benchoua A., Couriaud C., Chevalier E., et al. (2002) High sensitivity of protoplasmic cortical astroglia to focal ischemia. J. Cereb. Blood Flow Metab. 22, 289-298.
208. Hemmer K., Fransen L., Vanderstichele H., Vanmechelen E., and Heuschling P. (2001) An in vitro model for the study of microglia-induced neurodegeneration: involvement of nitric oxide and tumor necrosis factor-alpha. Neurochem. Int. 38, 557-565.
209. Velier J. J., Ellison J. A., Kikly K. K., Spera P. A., Barone F. C., and Feuerstein G. Z. (1999) Caspase-8 and caspase-3 are expressed by different populations of cortical neurons undergoing delayed cell death after focal stroke in the rat. J. Neurosci. 19, 5932-5941.
210. Salvesen G. S. and Dixit V. M. (1997) Caspases: intracellular signaling by proteolysis. Cell 91, 443-446.
211. Scaffidi C., Fulda S., Srinivasan A., Friesen C., Li F., Tomaselli K. J., et al. (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 17, 1675-1687.
212. Li H., Zhu H., Xu C. J., and Yuan J. (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501.
213. Shimizu S. and Tsujimoto Y. (2000) Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity. Proc. Natl. Acad. Sci. USA 97, 577-582.
214. Cerretti D. P., Kozlosky C. J., Mosley B., Nelson N., Van Ness K., Greenstreet T. A., et al. (1992) Molecular cloning of the interleukin-1 beta converting enzyme. Science 256, 97-100.
215. Yuan J., Shaham S., Ledoux S., Ellis H. M., and Horvitz H. R. (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641-652.
216. Enari M., Talanian R. V., Wong W. W., and Nagata S. (1996) Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature 380, 723-726.
217. Van de Craen M., Declercq W., Van den brande I., Fiers W., and Vandenabeele P. (1999) The proteolytic procaspase activation network: an in vitro analysis. Cell Death Differ. 6, 1117-1124.
218. Bhat R. V., DiRocco R., Marcy V. R., Flood D. G., Zhu Y., Dobrzanski P., et al. (1996) Increased expression of IL-1beta converting enzyme in hippocampus after ischemia: selective localization in microglia. J. Neurosci. 16, 4146-4154.
219. Rabuffetti M., Sciorati C., Tarozzo G., Clementi E., Manfredi A. A., and Beltramo M. (2000) Inhibition of caspase-1-like activity by Ac-Tyr-Val-Ala-Asp-chloromethyl ketone induces long-lasting neuroprotection in cerebral ischemia through apoptosis reduction and decrease of proinflammatory cytokines. J. Neurosci. 20, 4398-4404.
220. Hayashi Y., Jikihara I., Yagi T., Fukumura M., Ohashi Y., Ohta Y., et al. (2001) Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor in delayed neuronal death after transient cerebral ischemia. Brain Res. 893, 113-120.
221. Hara H., Fink K., Endres M., Friedlander R. M., Gagliardini V., Yuan J., et al. (1997) Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. J. Cereb. Blood Flow Metab. 17, 370-375.
222. Schielke G. P., Yang G. Y., Shivers B. D., and Betz A. L. (1998) Reduced ischemic brain injury in interleukin-1 beta converting enzyme-deficient mice. J. Cereb. Blood Flow Metab. 18, 180-185.
223. Yang G. Y., Schielke G. P., Gong C., Mao Y., Ge H. L., Liu X. H., et al. (1999) Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1 beta converting enzyme deficient mice. J. Cereb. Blood Flow Metab. 19, 1109-1117.
224. Schotte P., Van Criekinge W., Van de Craen M., Van Loo G., Desmedt M., Grooten J., et al. (1998) Cathepsin B-mediated activation of the proinflammatory caspase-11. Biochem. Biophys. Res. Commun. 251, 379-387.
225. Nitatori T., Sato N., Waguri S., Karasawa Y., Araki H., Shibanai K., et al. (1995) Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J. Neurosci. 15, 1001-1011.
226. Hill I. E., Preston E., Monette R., and MacManus J. P. (1997) A comparison of cathepsin B processing and distribution during neuronal death in rats following global ischemia or decapitation necrosis. Brain Res. 751, 206-216.
227. Yamashima T., Kohda Y., Tsuchiya K., Ueno T., Yamashita J., Yoshioka T., et al. (1998) Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'. Eur. J. Neurosci. 10, 1723-1733.
228. Seyfried D. M., Veyna R., Han Y., Li K., Tang N., Betts R. L., et al. (2001) A selective cysteine protease inhibitor is non-toxic and cerebroprotective in rats undergoing transient middle cerebral artery ischemia. Brain Res. 901, 94-101.
229. Tsuchiya K., Kohda Y., Yoshida M., Zhao L., Ueno T., Yamashita J., et al. (1999) Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors. Exp. Neurol. 155, 187-194.
230. Rao R. V., Hermel E., Castro-Obregon S., del Rio G., Ellerby L. M., Ellerby H. M., et al. (2001) Coupling endoplasmic reticulum stress to the cell death program. mechanism of caspase activation. J. Biol. Chem. 276, 33,869-33,874.
231. Yoneda T., Imaizumi K., Oono K., Yui D., Gomi F., Katayama T., et al. (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J. Biol. Chem. 276, 13,935-13,940.
232. Nakagawa T. and Yuan J. (2000) Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J. Cell Biol. 150, 887-894.
233. Deshmukh M. and Johnson E. M., Jr. (1997) Programmed cell death in neurons: focus on the pathway of nerve growth factor deprivation-induced death of sympathetic neurons. Mol. Pharmacol. 51, 897-906.
234. Xu D., Bureau Y., McIntyre D. C., Nicholson D. W., Liston P., Zhu Y., et al. (1999) Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus. J. Neurosci. 19, 5026-5033.
235. Namura S., Zhu J., Fink K., Endres M., Srinivasan A., Tomaselli K. J., et al. (1998) Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J. Neurosci. 18, 3659-3668.
236. Chen J., Nagayama T., Jin K., Stetler R. A., Zhu R. L., Graham S. H., et al. (1998) Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. J. Neurosci. 18, 4914-4928.
237. Endres M., Namura S., Shimizu-Sasamata M., Waeber C., Zhang L., Gomez-Isla T., et al. (1998) Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J. Cereb. Blood Flow Metab. 18, 238-247.
238. Tamatani M., Ogawa S., and Tohyama M. (1998) Roles of Bcl-2 and caspases in hypoxia-induced neuronal cell death: a possible neuroprotective mechanism of peptide growth factors. Brain Res. Mol. Brain Res. 58, 27-39.
239. Fink K., Linmin Z., 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.
240. Schulz J. B., Weller M., Matthews R. T., Heneka M. T., Groscurth P., Martinou J. C., et al. (1998) Extended therapeutic window for caspase inhibition and synergy with MK-801 in the treatment of cerebral histotoxic hypoxia. Cell Death Differ. 5, 847-857.
241. Gillardon F., Bottiger B., Schmitz B., Zimmermann M., and Hossmann K. A. (1997) Activation of CPP-32 protease in hippocampal neurons following ischemia and epilepsy. Brain Res. Mol. Brain Res. 50, 16-22.
242. Ni B., Wu X., Su Y., Stephenson D., Smalstig E. B., Clemens J., et al. (1998) Transient global forebrain ischemia induces a prolonged expression of the caspase-3 mRNA in rat hippocampal CA1 pyramidal neurons. J. Cereb. Blood Flow Metab. 18, 248-256.
243. 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.
244. Ouyang Y. B., Tan Y., Comb M., Liu C. L., Martone M. E., Siesjo B. K., et al. (1999) Survival-and death-promoting events after transient cerebral ischemia: phosphorylation of Akt, release of cytochrome C and Activation of caspase-like proteases. J. Cereb. Blood Flow Metab. 19, 1126-1135.
245. Himi T., Ishizaki Y., and Murata S. (1998) A caspase inhibitor blocks ischemia-induced delayed neuronal death in the gerbil. Eur. J. Neurosci. 10, 777-781.
246. Li H., Colbourne F., Sun P., Zhao Z., Buchan A. M., and Iadecola C. (2000) Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats. Stroke 31, 176-182.
247. Harrison D. C., Davis R. P., Bond B. C., Campbell C. A., James M. F., Parsons A. A., et al. (2001) Caspase mRNA expression in a rat model of focal cerebral ischemia. Brain Res. Mol. Brain Res. 89, 133-146.
248. Banasiaka K. J., Xiab Y., and Haddadbc G. G. (2000) Mechanisms underlying hypoxia-induced neuronal apoptosis. Prog. Neurobiol. 62, 215-249.
249. Lindsay R. M., Wiegand S. J., Altar C. A., and DiStefano P. S. (1994) Neurotrophic factors: from molecule to man. Trends Neurosci. 17, 182-190.
250. Lindvall O., Kokaia Z., Bengzon J., Elmer E., and Kokaia M. (1994) Neurotrophins and brain insults. Trends Neurosci. 17, 490-496.
251. Abe K. (2000) Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury. J. Cereb Blood Flow Metab. 20, 1393-1408.
252. Majdan M., Walsh G. S., Aloyz R., and Miller F. D. (2001) TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. J. Cell Biol. 155, 1275-1285.
253. Franke T. F., Kaplan D. R., and Cantley L. C. (1997) PI3K: downstream AKTion blocks apoptosis. Cell 88, 435-437.
254. Datta S. R., Dudek H., Tao X., Masters S., Fu H., Gotoh Y., et al. (1997) Akt phosphorylation of BAD couples survival signals to the cellintrinsic death machinery. Cell 91, 231-241.
255. del Peso L., Gonzalez-Garcia M., Page C., Herrera R., and Nunez G. (1997) Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278, 687-689.
256. Zha H. and Reed J. C. (1997) Heterodimerization-independent functions of cell death regulatory proteins Bax and Bcl-2 in yeast and mammalian cells. J. Biol Chem. 272, 31,482-31,489.
257. Rokudai S., Fujita N., Hashimoto Y., and Tsuruo T. (2000) Cleavage and inactivation of anti-apoptotic Akt/PKB by caspases during apoptosis. J. Cell Physiol. 182, 290-296.
258. Brunet A., Bormi A., Zigmond M. J., Lin M. Z., Juo P., Hu L. S., et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857-868.
259. Bachelder R. E., Wendt M. A., Fujita N., Tsuruo T., and Mercurio A. M. (2001) The cleavage of Akt/protein kinase B by death receptor signaling is an important event in detachment-induced apoptosis. J. Biol. Chem. 276, 34,702-34,707.
260. Dechant G., Tsoulfas P., Parada L. F., and Barde Y. A. (1997) The neurotrophin receptor p75 binds neurotrophin-3 on sympathetic neurons with high affinity and specificity. J. Neurosci. 17, 5281-5287.
261. Barde Y. A. (1989) Trophic factors and neuronal survival. Neuron 2, 1525-1534.
262. Snider W. D. (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627-638.
263. Bui N. T., Konig H. G., Culmsee C., Bauerbach E., Poppe M., Krieglstein J., et al. (2002) p75 neurotrophin receptor is required for constitutive and NGF-induced survival signalling in PC12 cells and rat hippocampal neurones. J. Neurochem. 81, 594-605.
264. Griffiths E. J. and Halestrap A. P. (1991) Further evidence that cyclosporin A protects mitochondria from calcium overload by inhibiting a matrix peptidyl-prolyl cis-trans isomerase. Implications for the immunosuppressive and toxic effects of cyclosporin. Biochem. J. 274, 611-614.
265. Lemaire C., Andreau K., Souvannavong V., and Adam A. (1998) Inhibition of caspase activity induces a switch from apoptosis to necrosis. FEBS Lett. 425, 266-270.
266. Nicotera P., Leist M., and Ferrando-May E. (1999) Apoptosis and necrosis: different execution of the same death. Biochem. Soc. Symp. 66, 69-73.
267. Hartmann A., Troadec J. D., Hunot S., Kikly K., Faucheux B. A., Mouatt-Prigent A., et al. (2001) Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson's disease, but pathway inhibition results in neuronal necrosis. J. Neurosci. 21, 2247-2255.
268. Deveraux Q. L. and Reed J. C. (1999) IAP family proteins - suppressors of apoptosis. Genes Dev. 13, 239-252.
269. Deveraux Q. L., Takahashi R., Salvesen G. S., and Reed J. C. (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388, 300-304.
270. Roy N., Deveraux Q. L., Takahashi R., Salvesen G. S., and Reed J. C. (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J. 16, 6914-6925.
271. Xu D. G., Crocker S. J., Doucet J. P., St-Jean M., Tamai K., Hakim A. M., et al. (1997) Elevation of neuronal expression of NAIP reduces ischemic damage in the rat hippocampus. Nat. Med. 3, 997-1004.
272. Xue D. and Horvitz H. R. (1995) Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein. Nature 377, 248-251.
273. Snipas S. J., Stennicke H. R., Riedl S., Potempa J., Travis J., Barrett A. J., et al. (2001) Inhibition of distant caspase homologues by natural caspase inhibitors. Biochem. J. 357, 575-580.
274. Shibata M., Hisahara S., Hara H., Yamawaki T, Fukuuchi Y., Yuan J., et al. (2000) Caspases determine the vulnerability of oligodendrocytes in the ischemic brain [In Process Citation]. J. Clin. Investig. 106, 643-653.
275. Tschopp J., Irmler M., and Thome M. (1998) Inhibition of fas death signals by FLIPs. Curr. Opin. Immunol. 10, 552-558.
276. Inohara N., Koseki T., Hu Y., Chen S., and Nunez G. (1997) CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Proc. Natl. Acad. Sci. USA 94, 10,717-10,722.
277. Cheema Z. F., Wade S. B., Sara M., Walsh K., Sohrabji F., and Miranda R. C. (1999) Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB. J. Neurosci. 19, 1754-1770.
278. Raoul C., Henderson C. E., and Pettmann B. (1999) Programmed cell death of embryonic motoneurons triggered through the Fas death receptor. J. Cell Biol. 147, 1049-1062.
279. Rasper D. M., Vaillancourt J. P., Hadano S., Houtzager V. M., Seiden I., Keen S. L., et al. (1998) Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Cell Death Differ. 5, 271-288.
280. Deckwerth T. L., Elliott J. L., Knudson C. M., Johnson E. M., Jr., Snider W. D., and Korsmeyer S. J. (1996) BAX is required for neuronal death after trophic factor deprivation and during development. Neuron 17, 401-411.
281. Shigeno T., Mima T., Takakura K., Graham D. I., Kato G., Hashimoto Y., et al. (1991) Amelioration of delayed neuronal death in the hippocampus by nerve growth factor. J. Neurosci. 11, 2914-2919.
282. Andsberg G., Kokaia Z., Bjorklund A., Lindvail O., and Martinez-Serrano A. (1998) Amelioration of ischaemia-induced neuronal death in the rat striatum by NGF-secreting neural stem cells. Eur. J. Neurosci. 10, 2026-2036.
283. Pechan P. A., Yoshida T., Panahian N., Moskowitz M. A., and Breakefield X. O. (1995) Genetically modified fibroblasts producing NGF protect hippocampal neurons after ischemia in the rat. Neuroreport 6, 669-672.
284. Hefti F. (1994) Neurotrophic factor therapy for nervous system degenerative diseases. J. Neurobiol. 25, 1418-1435.
285. Dijkhuizen P. A. and Verhaagen J. (1999) The use of neurotrophic factors to treat spinal cord injury: advantages and disadvantages of different delivery methods. Neurosci. Res. Comm. 24, 1-9.
286. Eriksdotter-Jonhagen M., Nordberg A., Amberla K., Backman L., Ebendal T., Meyerson B., et al. (1998) Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 9, 246-257.
287. Trafermin (1999). CAB 2001, KCB 1, Fiblast. Drugs R.D. 1, 40-41.
288. Semkova I., Wolz P., Schilling M., and Krieglstein J. (1996) Selegiline enhances NGF synthesis and protects central nervous system neurons from excitotoxic and ischemic damage. Eur. J. Pharmacol. 315, 19-30.
289. Seniuk N. A., Henderson J. T., Tatton W. G., and Roder J. C. (1994) Increased CNTF gene expression in process-bearing astrocytes following injury is augmented by R(-)-deprenyl. J. Neurosci. Res. 37, 278-286.
290. Culmsee C., Stumm R. K., Schafer M. K., Weihe E., and Krieglstein J. (1999) Clenbuterol induces growth factor mRNA, activates astrocytes, and protects rat brain tissue against ischemic damage. Eur. J. Pharmacol. 379, 33-45.
291. Waschek J. A., Dicicco-Bloom E. M., Lelievre V., Zhou X., and Hu Z. (2000) PACAP action in nervous system development, regeneration, and neuroblastoma cell proliferation. Ann. NY Acad. Sci. 921, 129-136.
292. Lu N., Zhou R., and DiCicco-Bloom E. (1998) Opposing mitogenic regulation by PACAP in sympathetic and cerebral cortical precursors correlates with differential expression of PACAP receptor (PAC1-R) isoforms. J. Neurosci. Res. 53, 651-662.
293. Vaudry D., Gonzalez B. J., Basille M., Yon L., Foumier A., and Vaudry H. (2000) Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol. Rev. 52, 269-324.
294. Banks W. A., Uchida D., Arimura A., Somogyvari-Vigh A., and Shioda S. (1996) Transport of pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier and the prevention of ischemia-induced death of hippocampal neurons. Ann NY Acad. Sci. 805, 270-277; discussion 277-279.
295. Arimura A., Somogyvari-Vigh A., Weill C., Fiore R. C., Tatsuno I., Bay V., et al. (1994) PACAP functions as a neurotrophic factor. Ann. NY Acad. Sci. 739, 228-243.
296. Uchida D., Arimura A., Somogyvari-Vigh A., Shioda S., and Banks W. A. (1996) Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide. Brain Res. 736, 280-286.
297. Jones T. A. and Schallert T. (1994) Use-dependent growth of pyramidal neurons after neocortical damage. J. Neurosci. 14, 2140-2152.
298. Defer G. L., Geny C., Ricolfi F., Fenelon G., Monfort J. C., Remy P., et al. (1996) Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach. Brain 119, 41-50.
299. Palfi S., Conde F., Riche D., Brouillet E., Dautry C., Mittoux V., et al. (1998) Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington disease. Nat. Med. 4, 963-966.
300. Dunnett S. B. and Bjorklund A. (1999) Prospects for new restorative and neuroprotective treatments in Parkinson's disease. Nature 399, A32-A39.
301. Hagell P., Schrag A., Piccini P., Jahanshahi M., Brown R., Rehncrona S., et al. (1999) Sequential bilateral transplantation in Parkinson's disease: effects of the second graft. Brain 122, 1121-1132.
302. Bjorklund A. and Lindvall O. (2000) Cell replacement therapies for central nervous system disorders. Nat. Neurosci. 3, 537-544.
303. Svendsen C. N. and Smith A. G. (1999) New prospects for human stem-cell therapy in the nervous system. Trends Neurosci. 22, 357-364.
304. Bjorklund A. and Svendsen C. (1999) Stem cells. Breaking the brain-blood barrier. Nature 397, 569-570.
305. Eriksson P. S., Perfilieva E., Bjork-Eriksson T., Alborn A. M., Nordborg C., Peterson D. A., et al. (1998) Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313-1317.
306. Altman J. (1962) Are new neurons formed in the brain of adult mammalians? Science 135, 1127-1128.
307. Nottebohm F. (2002) Why are some neurons replaced in adult brain? J. Neurosci. 22, 624-628.
308. Altman J. and Das G. (1965) Autoradiographic and histological evidence of postnatal neurogenesis in rats. J. Comp. Neurol. 124, 319-335.
309. Kaplan M. S. and Hinds J. W. (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197, 1092-1094.
310. Cameron H. A., Woolley C. S., McEwen B. S., and Gould E. (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56, 337-344.
311. Gage F. H., Ray J., and Fisher L. J. (1995) Isolation, characterization, and use of stem cells from the CNS. Annu. Rev. Neurosci. 18, 159-192.
312. Palmer T. D., Takahashi J., and Gage F. H. (1997) The adult rat hippocampus contains primordial neural stem cells. Mol. Cell. Neurosci. 8, 389-404.
313. Richards L. J., Kilpatrick T. J., and Bartlett P. F. (1992) De novo generation of neuronal cells from the adult mouse brain. Proc. Natl. Acad. Sci. USA 89, 8591-8595.
314. Reynolds B. A. and Weiss S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707-1710.
315. Lois C. and Alvarez-Buylla A. (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145-1148.
316. Seki T. and Arai Y. (1993) Highly polysialylated neural cell adhesion molecule (NCAMH) is expressed by newly generated granule cells in the dentate gyms of the adult rat. J. Neurosci. 13, 2351-2358.
317. Altman J. (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J. Comp. Neurol. 137, 433-457.
318. Doetsch F., Garcia-Verdugo J., and Alvarez-Buylla A. (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17, 5046-5061.
319. McKay R. (1997) Stem cells in the central nervous system. Science 276, 66-71.
320. Seri B., Garcia-Verdugo J. M., McEwen B. S., and Alvarez-Buylla A. (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J. Neurosci. 21, 7153-7160.
321. Palmer T. D., Ray J., and Gage F. H. (1995) FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain. Mol. Cell. Neurosci. 6, 474-486.
322. Kondo T. and Raff M. (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 1754-1757.
323. Shihabuddin L. S., Horner P. J., Ray J., and Gage F. H. (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J. Neurosci. 20, 8727-8735.
324. Benraiss A., Chmielnicki E., Lerner K., Roh D., and Goldman S. A. (2001) Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J. Neurosci. 21, 6718-6731.
325. Gould E. and Gross C. G. (2002) Neurogenesis in adult mammals: some progress and problems. J. Neurosci. 22, 619-623.
326. Nilsson M., Perfilieva E., Johansson U., Orwar O., and Eriksson P. S. (1999) Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J. Neurobiol. 39, 569-578.
327. Rochefort C., Gheusi G., Vincent J. D., and Lledo P. M. (2002) Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory. J. Neurosci. 22, 2679-2689.
328. Gould E., McEwen B. S., Tanapat P., Galea L. A., and Fuchs E. (1997) Neurogenesis in the dentate gyms of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci. 17, 2492-2498.
329. Tanapat P., Hastings N. B., Rydel T. A., Galea L. A., and Gould E. (2001) Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism. J. Comp. Neurol. 437, 496-504.
330. Galea L. A. and McEwen B. S. (1999) Sex and seasonal differences in the rate of cell proliferation in the dentate gyrus of adult wild meadow voles. Neuroscience 89, 955-964.
331. van Praag H., Kempermann G., and Gage F. H. (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266-270.
332. Kempermann G., Kuhn H. G., and Gage F. H. (1997) Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc. Natl. Acad. Sci. USA 94, 10,409-10,414.
333. Snyder E. Y., Yoon C., Flax J. D., and Macklis J. D. (1997) Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex. Proc. Natl. Acad. Sci. USA 94, 11,663-11,668.
334. Parent J. M., Janumpalli S., McNamara J. O., and Lowenstein D. H. (1998) Increased dentate granule cell neurogenesis following amygdala kindling in the adult rat. Neurosci. Lett. 247, 9-12.
335. Parent J. M., Valentin V. V., and Lowenstein D. H. (2002) Prolonged seizures increase proliferating neuroblasts in the adult rat subventricular zone-olfactory bulb pathway. J. Neurosci. 22, 3174-3188.
336. Madsen T. M., Treschow A., Bengzon J., Bolwig T. G., Lindvall O., and Tingstrom A. (2000) Increased neurogenesis in a model of electro-convulsive therapy. Biol. Psychiatry 47, 1043-1049.
337. Jin K., Minami M., Lan J. Q., Mao X. O., Batteur S., Simon R. P., et al. (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc. Natl. Acad. Sci. USA 98, 4710-4715.
338. Takagi Y., Nozaki K., Takahashi J., Yodoi J., Ishikawa M., and Hashimoto N. (1999) Proliferation of neuronal precursor cells in the dentate gyms is accelerated after transient forebrain ischemia in mice. Brain Res. 831, 283-287.
339. Jiang W., Gu W., Brannstrom T., Rosqvist R., and Wester P. (2001) Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion. Stroke 32, 1201-1207.
340. Liu J., Solway K., Messing R. O., and Sharp F. R. (1998) Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J. Neurosci. 18, 7768-7778.
341. Sharp F. R., Liu J., and Bernabeu R. (2002) Neurogenesis following brain ischemia. Brain Res. Dev. Brain Res. 134, 23-30.
342. Park K. I. (2000) Transplantation of neural stem cells: cellular &
343. Lim D. A., Tramontin A. D., Trevejo J. M., Herrera D. G., Garcia-Verdugo J. M., and Alvarez-Buylla A. (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713-726.
344. Alvarez-Buylla A and Garcia-Verdugo J. M. (2002) Neurogenesis in adult subventricular zone. J. Neurosci. 22, 629-634.
345. Dunnett S. and Björklund A. (1994) Functional Neural Transplantation, vol. 2, Raven, New York, pp. 103-138.
346. Bachoud-Levi A. C., Remy P., Nguyen J. P., Brugieres P., Lefaucheur J. P., Bourdet C., et al. (2000) Motor and cognitive improvements in patients with Huntington's disease after neural transplantation. Lancet 356, 1975-1979.
347. Aoki H., Onodera H., Yae T., Jian Z., and Kogure K. (1993) Neural grafting to ischemic CA1 lesions in the rat hippocampus: an autoradiographic study. Neuroscience 56, 345-354.
348. Hodges H., Nelson A., Virley D., Kershaw T. R., and Sinden J. D. (1997) Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy. Pharmacol. Biochem. Behav. 56, 763-780.
349. Szele F. G. and Chesselet M. F. (1996) Cortical lesions induce an increase in cell number and PSA-NCAM expression in the subventricular zone of adult rats. J. Camp. Neurol. 368, 439-454.
350. Aubert I., Rider J. L., Schachner M., Rougon G., and Gage F. H. (1998) Expression of L1 and PSA during sprouting and regeneration in the adult hippocampal formation. J. Comp. Neurol. 399, 1-19.
351. Hayashi T., Seki T., Sato K., Iwai M., Zhang W. R., Manabe Y., et al. (2001) Expression of polysialylated neural cell adhesion molecule in rat brain after transient middle cerebral artery occlusion. Brain Res. 907, 130-133.
352. Sinden J. D., Rashid-Doubell F., Kershaw T. R., Nelson A., Chadwick A., Jar P. S., et al. (1997) Recovery of spatial learning by grafts of a conditionally immortalized hippocampal neuroepithelial cell line into the ischaemia-lesioned hippocampus. Neuroscience 81, 599-608.
353. Kondziolka D., Wechsler L., Goldstein S., Meltzer C., Thulborn K. R., Gebel J., et al. (2000) Transplantation of cultured human neuronal cells for patients with stroke. Neurology 55, 565-569.
354. Morshead C. M., Reynolds B. A., Craig C. G., McBurney M. W., Staines W. A., Morassutti D., et al. (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13, 1071-1082.
355. Laywell E. D., Rakic P., Kukekov V. G., Holland E. C., and Steindler D. A. (2000) Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc. Natl. Acad. Sci. USA 97, 13,883-13,888.
356. Duncan I. D. and Hoffman R. L. (1997) Schwann cell invasion of the central nervous system of the myelin mutants. J. Anat. 190, 35-49.
357. Spedding M. (2002) Reasons why stroke trials underestimate the neuroprotective effects of drugs. Stroke 33, 324-325.
358. Grotta J., Clark W., Coull B., Pettigrew L. C., Mackay B., Goldstein L. B., et al. (1995) Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial. Stroke 26, 602-605.
359. Davis S. M., Albers G. W., Diener H. C., Lees K. R., and Norris J. (1997) Termination of Acute Stroke Studies Involving Selfotel Treatment. ASSIST Steering Committed. Lancet 349, 32.
360. Merchant R. E., Bullock M. R., Carmack C. A., Shah A. K., Wilner K. D., Ko G., et al. (1999) A double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of CP-101,606 in patients with a mild or moderate traumatic brain injury. Ann. NY Acad. Sci. 890, 42-50.
361. Muir K. W. and Lees K. R. (1995) A randomized, double-blind, placebo-controlled pilot trial of intravenous magnesium sulfate in acute stroke. Stroke 26, 1183-1188.
362. Dyker A. G. and Lees K. R. (1999) Remacemide hydrochloride: a double-blind, placebo-controlled, safety and tolerability study in patients with acute ischemic stroke. Stroke 30, 1796-1801.
363. Albers G. W., Clark W. M., Atkinson R. P., Madden K., Data J. L., and Whitehouse M. J. (1999) Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. Stroke 30, 508-513.
364. Lees K. R., Asplund K., Carolei A., Davis S. M., Diener H. C., Kaste M., et al. (2000) Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial. GAIN International Investigators. Lancet 355, 1949-1954.
365. Limburg M. and Hijdra A. (1990) Flunarizine in acute ischemic stroke: a pilot study. Eur. Neurol. 30, 121-122.
366. Kassell N. F., Haley E. C., Jr., Apperson-Hansen C., and Alves W. M. (1996) Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J. Neurosurg. 84, 221-228.
367. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). The RANTTAS Investigators. Stroke 27, 1453-1458.
368. Haley E. C., Jr. (1998) High-dose tirilazad for acute stroke (RANTTAS II). RANTTAS II Investigators. Stroke 29, 1256-1257.
369. Wahlgren N. G., Ranasinha K. W., Rosolacci T., Franke C. L., van Erven P. M., Ashwood T., et al. (1999) Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 30, 21-28.