Clinical Trials For Cytoprotection In Stroke

NeuroRx

Volumn 1, Issue 1, 2004, Pages 46-70

  Labiche, Lise A ^a   Grotta, James C ^a  

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

clinical trials; ischemia; neuroprotection; Stroke; treatment

Indexed keywords

3 (5 CHLORO 2 METHOXYPHENYL) 3 FLUORO 2,3 DIHYDRO 6 TRIFLUOROMETHYL 1H INDOL 2 ONE; 4 PHOSPHONOMETHYLPIPECOLIC ACID; [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; ALTEPLASE; APTIGANEL; AR R15696; ARUNDIC ACID; CITICOLINE; CLOMETHIAZOLE; DEXTRORPHAN; DIAZEPAM; DISUFENTON SODIUM; ELIPRODIL; FOSPHENYTOIN SODIUM; GAVESTINEL; GLUTAMATE RECEPTOR ANTAGONIST; INTERCELLULAR ADHESION MOLECULE 1 ANTIBODY; LIFARIZINE; LUBELUZOLE; MAGNESIUM SULFATE; NALMEFENE; NALOXONE; NICARDIPINE; NIMODIPINE; REPINOTAN; ROVELIZUMAB; SIPATRIGINE; TACROLIMUS; TRAZODONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; NEUROPROTECTIVE AGENT;

AGITATION; ANEMIA; ARTICLE; ATAXIA; BLOOD CLOT LYSIS; BRAIN EDEMA; BRAIN HEMORRHAGE; CEREBROVASCULAR ACCIDENT; CEREBROVASCULAR DISEASE; CLINICAL TRIAL; COMA; COMBINATION CHEMOTHERAPY; CONFUSION; CONSTIPATION; CONTINUOUS INFUSION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DELIRIUM; DISEASE SEVERITY; DISORIENTATION; DIZZINESS; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG MEGADOSE; DYSARTHRIA; FEVER; HALLUCINATION; HEADACHE; HEART ARREST; HEART ATRIUM FIBRILLATION; HEART DISEASE; HEART INFARCTION; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPOTENSION; INDUCED HYPOTHERMIA; LIVER FUNCTION TEST; LOADING DRUG DOSE; LOW DRUG DOSE; LUNG EDEMA; MENINGITIS; META ANALYSIS; NAUSEA; NEUROIMAGING; NEUROLOGIC DISEASE; NEUROPROTECTION; NYSTAGMUS; PARANOIA; PARESTHESIA; PATIENT SELECTION; PNEUMONIA; QT PROLONGATION; REPERFUSION; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; SOMNOLENCE; STROKE; STUPOR; SYSTEMATIC REVIEW; URINARY TRACT INFECTION; VOMITING; ANIMAL; BRAIN; DRUG EFFECT; METHODOLOGY; REVIEW; TREATMENT OUTCOME;

ANIMALS; BRAIN; CEREBROVASCULAR ACCIDENT; CLINICAL TRIALS; HUMANS; NEUROPROTECTIVE AGENTS; RESEARCH DESIGN; TREATMENT OUTCOME;

EID: 13844258517     PISSN: 15455343     EISSN: 15455351     Source Type: Journal    
DOI: 10.1602/neurorx.1.1.46     Document Type: Article

References (232)

1. Bean B. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci USA 81 (1984) 6388-6392
2. Grotta J. Clinical aspects of the use of calcium antagonists in cerebrovascular disease. Clin Neuropharmacol 14 (1991) 373-390
3. Petruk K., West M., Mohr G., Weir B., Benoit B., Gentili F., et al. Nimodipine treatment in poor-grade aneurysm patients: results of a multicenter double-blind placebo-controlled trial. J Neurosurg 68 (1988) 505-517
4. Pickard J., Murray G., Illingworth R., Shaw M., Teasdale G., Foy P., et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 298 (1989) 636-642
5. Ohman J., Servo A., and Heiskanen O. Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery. J Neurosurg 74 (1991) 8-13
6. Barker F., and Ogilvy C. Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a meta-analysis. J Neurosurg 84 (1996) 405-414
7. Feigin V., Rinkel G., Algra A., Vermeulen M., and van Gijn J. Calcium antagonists for aneurismal subarachnoid haemorrhage. Cochrane Database Syst Rev (2000) CD000277
8. Gelmers H. The effects of nimodipine on the clinical course of patients with acute ischemic stroke. Acta Neurol Scand 69 (1984) 232-239
9. Paci A., Ottaviano P., Trenta A., Iannone G., DeSantis L., Lancia G., et al. Nimodipine in acute ischemic stroke: a double-blind controlled study. Acta Neurol Scand 80 (1989) 282-286
10. Gelmers H., and Hennerici M. Effect of nimodipine on acute ischemic stroke: Pooled results from 5 randomized trials. Stroke 21 Suppl 12 (1990) IV81-IV84
11. Nag D., Garg R., and Varma M. A randomized double-blind controlled study of nimodipine in acute cerebral ischemic stroke. Indian J Physiol (Lond) Pharmacol 42 (1998) 555-558
12. The American Nimodipine Study Group. Clinical trial of nimodipine in acute ischemic stroke. Stroke 23 (1992) 3-8
13. Wahlgren N., MacMahon D., De Keyser J., Ryman T., and INWEST Study Group. Intravenous Nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischemic stroke. Cerebrovasc Dis 4 (1994) 204-210
14. Kaste M., Fogelholm R., Erila T., et al. A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke. Stroke 25 (1994) 1348-1353
15. Ahmed N., Nasman P., and Wahlgren N. Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke 31 (2000) 1250-1255
16. Mohr J., Orgogozo J., Harrison M., Hennerici M., Wahlgren N., Gelmers J., et al. Meta-analysis of oral nimodipine trials in acute ischemic stroke. Cerebrovasc Dis 4 (1994) 197-203
17. Horn J., de Haan R., Verneulen M., and Limburg M. Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial. Stroke 32 (2001) 461-465
18. Rosenbaum D., Zabramski J., Frey J., Yatsu F., Marler J., Spetzler R., et al. Early treatment of ischemic stroke with a calcium antagonist. Stroke 22 (1991) 437-441
19. Koh J., and Cotman C. Programmed cell death: its possible contribution to neurotoxicity mediated by calcium channel antagonists. Brain Res 587 (1992) 233-240
20. Grotta J., Picone C., Ostrow P., Strong R., Earls R., Yao L., et al. CGS-19755, a competitive NMDA receptor antagonist, reduces calcium-calmodulin binding and improves outcome after global cerebral ischemia. Ann Neurol 27 (1990) 612-619
21. Simon R., and Shiraishi K. N-methyl-d-aspartate antagonist reduces stroke size and regional glucose metabolism. Ann Neurol 27 (1990) 606-611
22. Simmonds J., Sailer T., and Moyer J. The effects of CGS-19755 in rat focal cerebral ischemia produced by tandem ipsilateral common carotid artery and middle cerebral artery occlusion [abstract]. Soc Neurosci Abstr 19 (1993) 1647
23. Grotta J., Clark W., Coull B., Pettigrew L., Mackay B., Goldstein K., et al. Safety and tolerability of the glutamate antagonist CGS 1975 (selfotel) in patients with acute ischemic stroke: results of a phase IIa randomized trial. Stroke 26 (1995) 602-605
24. Davis S., Lees K., Albers G., Diener H., Markabi S., Karlsson G., and Norris J. Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31 (2000) 347-354
25. Steinberg G., Perez-Pinzon M., Maier C., et al. CGS-19755: correlation of in vitro neuroprotection, protection against experimental ischemia and CSF levels in cerebrovascular surgery patients. Abstract presented at Proceedings of the 5th International Symposium on Pharmacology of Cerebral Ischemia, Marburg, Germany (July 1994) 20-22
26. Albers G., Atkinson R., Kelley R., and Rosenbaum D. Safety, tolerability, and pharmacokinetics of the N-methyl-B-aspartate antagonist dextrorphan in patients with acute stroke. Stroke 26 (1995) 254-258
27. Minematsu K., Fisher M., Li L., Davis M., Knapp A., Cotter R., et al. Effects of a novel MNDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion-weighted MRI. Neurology 43 (1993) 397-403
28. Dyker A., Edwards K., Fayad P., Hormes J., and Lees K. Safety and tolerability study of aptiganel hydrochloride in patients with an acute ischemic stroke. Stroke 30 (1999) 2038-2042
29. Albers G., Goldstein L., Hall D., and for the Aptiganel Acute Stroke Investigators. Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial. JAMA 21 (2001) 2673-2682
30. Muir K. Magnesium in stroke treatment. Postgrad Med J 78 (2002) 641-645
31. Weglicki W., and Phillips T. Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis. Am J Physiol (Lond) 263 (1992) R734-R737
32. Yang Y., Li Q., Ahmad F., and Shuaib A. Survival and histological evaluation of therapeutic window of post-ischemia treatment with magnesium sulfate in embolic stroke model of rat. Neurosci Lett 285 (2000) 119-122
33. Muir K., and Lees D. A randomized, double-blind, placebo-controlled pilot trial of intravenous magnesium sulfate in acute stroke. Stroke 126 (1995) 1183-1188
34. Muir K., and Lees K. Dose optimization of intravenous magnesium sulfate after acute stroke. Stroke 29 (1998) 918-923
35. Izumi Y., Roussl S., Pinard E., and Seylaz J. Reduction of infarct volume by magnesium after middle cerebral artery occlusion in rates. J Cereb Blood Flow Metab 11 (1991) 1025-1030
36. Saver J., Kidwell C., Leary M., et al. The field administration of stroke therapy-magnesium (FAST-MAG) pilot trial. Abstract presented at the ongoing clinical trials session, 26th International Stroke Conference, Fort Lauderdale, FL (Feb 2001)
37. Olney J., Labruyere J., and Price M. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244 (1989) 1360-1362
38. Olney J., Wozniak D., Jevtovic-Todorovic V., Farber N., Bittigau P., and Ikonomidou C. Drug-induced apoptotic neurodegeneration in the developing brain. Brain Pathol 12 (2002) 488-498
39. Lees K. Cerestat and other NMDA antagonists in ischemic stroke. Neurology 49 Suppl 4 (1997) S66-S69
40. Bordi F., Pietra C., Ziviani L., and Reggiani A. The glycine antagonist GV150526 protects somatosensory evoked potentials and reduces the infarct area in the MCAO model of focal ischemia in the rat. Exp Neurol 145 (1997) 425-433
41. Dyker A. Lees KR. Safety and tolerability of GV150526 (a glycine site antagonist at the N-methyl-d-aspartate receptor) in patients with acute stroke. Stroke 30 (1999) 986-992
42. Sacco R., DeRosa J., Haley E., Levin B., Ordronneau P., Phillips S., et al., for the GAIN Americas Investigators. Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial. JAMA 285 (2001) 1719-1728
43. Lees K., Asplund K., Carolei A., Davis S., Diener H., Kaste H., et al., for the GAIN International Investigators. Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: A randomized controlled trial. Lancet 355 (2000) 1949-1954
44. Kawasaki-Yatsugi S., Ichiki C., Yatsugi S., Takahashi M., Shimizu-Sasamata M., Yamaguchi T., et al. Neuroprotective effects of an AMPA receptor antagonist YM872 in a rat transient middle cerebral artery occlusion model. Neuropharmacology 39 (2000) 211-217
45. Suzuki M., Sasamata M., and Miyata K. Neuroprotective effects of YM872 coadministered with t-PA in a rat embolic stroke model. Brain Res 959 (2003) 169-172
46. Smith S., and Meldrum B. Cerebroprotective effect of lamotrigine after focal ischemia in rats. Stroke 26 (1995) 117-121
47. Traystman R., Klaus J., DeVries A., Shaivitz A., and Hurn P. Anticonvulsant lamotrigine administered on reperfusion fails to improve experimental stroke outcomes. Stroke 32 (2001) 783-787
48. Leach M., Swan J., Eisenthal D., Dopson M., and Nobbs M. BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage. Stroke 24 (1993) 1063-1067
49. Kawaguchi K., and Graham S. Neuroprotective effects of the glutamate release inhibitor 619C89 in temporary middle cerebral artery occlusion. Brain Res 749 (1991) 131-134
50. Muir K., Holzapfel L., and Lees K. Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke. Cerebrovasc Dis 10 (2000) 431-436
51. Sipatrigine in Stroke (SIS). Stroke Center Clinical Trials Directory. http://www.strokecenter.org/trials/TrialDetail.asp?ref=276&browse=ac ute [updated 7/3/2002]
52. Fosphenytoin Phase 3. Stroke Center Clinical Trials Directory. http://www.strokecenter.org/trials/TrialDetail.asp?ref=218&browse=ac ute [updated 8/3/2000]
53. Gribkoff V., Starrett J., and Dworetzky S. The pharmacology and molecular biology of large-conductance calcium-activated (BK) potassium channels. Adv Pharmacol 37 (1997) 319-348
54. Bozik M., Hommel M., Grotta J., et al. Efficacy and safety of MaxiPost in patients with acute stroke [abstract]. JNS 187 (2001) S252
55. DeRyck M., Keersmaekers R., Clincke G., Janssen M., and VanReet S. Lubeluzole, a novel benzothiazole, protects neurologic function after cerebral thrombotic stroke in rats: an apparent stereospecific effect [abstract]. Soc Neurosci Abstr 20 (1994) 185
56. Aronowski J., Strong R., and Grotta J. Treatment of experimental focal ischemia in rats with lubeluzole. Neuropharmacology 35 (1996) 689-693
57. DeRyck M., Verhoye M., and Van der Linden A. Diffusion-weighted MRI of infarct growth in a rat photochemical stroke model: effect of lubeluzole. Neuropharmacology 39 (2000) 691-702
58. Scheller D., De Ryck M., Kolb J., Szathmary S., van Reempts J., Clincke G., et al. Lubeluzole blocks increases in extracellular glutamate and taurine in the peri-infarct zone in rats. Eur J Pharmacol 338 (1997) 243-251
59. Lesage A., Peeters L., and Leysen J. Lubeluzole, a novel long-term neuroprotectant, inhibits the glutamate-activated nitric oxide synthase pathway. J Pharmacol Exp Ther 279 (1996) 759-766
60. Diener H., Hacke W., Hennerici M., Radberg J., Hautson L., De Keyser J., and for the Lubeluzole International Study Group. Lubeluzole in acute ischemic stroke: a double-blind placebo controlled phase II trial. Stroke 27 (1996) 76-81
61. DeRyck M., Keersmackers R., Duytschaever H., Claes C., Clicke G., and Janssen M. Lubeluzole protects sensorimotorfunction and reduces infarct size in a photochemical stroke model. J Pharmacol Exp Ther 35 (1996) 748-758
62. Diener H. Multinational randomized controlled trial of lubeluzole in acute ischaemic stroke: European and Australian Lubeluzole Ischaemic Stroke Study Group. Cerebrovasc Dis 8 (1998) 172-181
63. Grotta J., and for the US and Canadian Lubeluzole Ischemic Stroke Study Group. Lubeluzole treatment of acute ischemic stroke. Stroke 28 (1997) 2338-2346
64. Grotta J. Combination Therapy Stroke Trial: Recombinant tissue-type plasminogen activator with/without lubeluzole. Cerebrovasc Dis 12 (2001) 258-263
65. Gandolfo C., Sandercock P., and Conti M. Lubeluzole for acute ischaemic stroke. Cochrane Database Syst Rev (2002) CD001924
66. Davies M., Deisz R., Prince D., and Peroutka S. Two distinct effects of 5-hydroxytryptamine on single cortical neurons. Brain Res 423 (1987) 347-352
67. Schaper C., Zhu Y., Kouklei M., Culmsee C., and Krieglstein J. Stimulation of 5-HT1A receptors reduces apoptosis after transient forebrain ischemia in the rat. Brain Res 883 (2000) 41-50
68. Ramirez-Lessepas M., Patrick B., Snyder B., and Lakatua D. Failure of central nervous system serotonin blockage to influence outcome in acute cerebral infarction: a double-blind randomized trial. Stroke 17 (1986) 953-956
69. Semkova I., Wolz P., and Krieglstein J. Neuroprotective effect of 5-HT1A receptor agonist, BAY x 3702, demonstrated in vitro and in vivo. Eur J Pharmacol 359 (1998) 251
70. Bayer Randomized Acute Ischemia Neuroprotectant Study (BRAINS). Abstracts from the 4th World Stroke Congress. Stroke 31 (2000) 2768
71. Teal P, Rombout F, Weber H, et al., Repinotan (BAY x 3702) in acute ischemic stroke: a randomized exposure controlled trial. Abstract presented in the Ongoing Clinical Trials Session, 26th International Stroke Conference, Fort Lauderdale, FL, February, 2001
72. ONO-2506 in Acute Ischemic Stroke. Stroke Center Clinical Trials Directory. http://www.strokecenter.org/trials/TrialDetail.asp?ref=469&browse=ac ute [updated 11/14/2002]
73. Harini R., Supra E., Roberts J., and Lavyne M. Effect of naloxone on cerebral perfusion and cardiac performance during experimental cerebral ischemia. J Neurosurg 64 (1986) 780-786
74. Namba S., Nishigaki S., Fujiwara N., Wani T., Namba Y., and Masaoka T. Opiate-antagonist reversal of neurological deficits: experimental and clinical studies. Jpn J Psychiatry Neurol 40 (1986) 61-79
75. Baskin D., Juroda H., Hosobuchi Y., and Lee N. Treatment of Stroke with optiate antagonists-effects of exogenous antagonist and synorphin 1-13. Neuropeptides 5 (1987) 307-310
76. Fallis R., Fisher M., and Lobo R. A double-blind trial of naloxone in the treatment of acute stroke. Stroke 15 (1984) 627-629
77. Jabaily J., and Davis J. Naloxone administration to patients with acute stroke. Stroke 15 (1984) 36-39
78. Adams Jr. H., Olinger C., Barsan W., Butler M., Graff-Radford N., Brott T., et al. A dose-escalation study of large doses of naloxone for treatment of patients with acute cerebral ischemia. Stroke 17 (1986) 404-409
79. Olinger C., Adams Jr. H., Brott T., Biller J., Barsan W., Toffol G., et al. High-dose intravenous naloxone for the treatment of acute ischemic stroke. Stroke 21 (1990) 721-725
80. Federico F., Lucivero V., Lamberti P., Fiore A., and Conte C. A double blind randomized pilot trial of naloxone in the treatment of acute ischemic stroke. Ital J Neurol Sci 12 (1991) 557-563
81. Clark W., Coull B., Karukin M., Hendin B., Kelly B., Rosing H., et al. Randomized trial of Cervene, a κ receptor-selective opioid antagonist, in acute ischemic stroke. J Stroke Cerebrovasc Dis 6 (1996) 35-40
82. Clark W., Ertag W., Orecchio E., and Raps E. Cervene in acute ischemic stroke: results of a double-blind, placebo-controlled, dose-comparison study. J Stroke Cerebrovasc Dis 8 (1999) 224-230
83. Clark W., Raps E., Tong D., Kelly R., and for the Cervene Stroke Study Investigators. Cervene (nalmefene) in acute ischemic stroke: final results of a phase III efficacy study. Stroke 31 (2000) 1234-1239
84. Green A., Hainsworth A., and Jackson D. GABA potentiation: a logical pharmacological approach for the treatment of acute ischaemic stroke. Neuropharmacology 39 (2000) 1483-1494
85. Moody I., and Skolnick P. Clomethiazole: neurochemical actions at the gamma-aminobutyric acid complex. Br J Pharmacol 164 (1989) 153-158
86. Cross A., Jones J., Baldwin H., and Green A. Neuroprotective activity of clomethiazole following transient forebrain ischemia in the gerbil. Br J Pharmacol 104 (1991) 406-411
87. Marshall J., Cross A., Murray T., and Ridley R. Functional benefit from clomethiazole treatment after focal cerebral ischaemia in a non-human primate species [abstract]. Stroke 29 (1998) 330
88. Wester P., Strand T., Wahlgren N., Ashwood T., and Osswald G. An open study of clomethiazole in patients with acute cerebral infarction. Cerebrovasc Dis 8 (1998) 188-190
89. Sydserff S., Cross A., Murray T., Jones J., Green A., et al. Clomethiazole is neuroprotective in models of global and focal cerebral ischemia when infused at doses producing clinically relevant plasma concentrations. Brain Res 862 (2000) 59-62
90. Wahlgren N., Ranasinha K., Rosolacci T., Franke C., van Erven P., Ashwood T., et al., for the CLASS Study Group. Clonethiazole Acute Stroke Study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 30 (1999) 21-28
91. Wahlgren N., Diez-Tejedor E., Teitelbaum J., Arboix A., Leys D., Ashwood T., et al., for the CLASS Study Group. Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients. Stroke 31 (2000) 82-85
92. Lyden P., Shuaib A., Ng K., Levin K., Atkinson R., Rajput A., et al. The CLASS-I/H/T Investigators: Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results. Stroke 33 (2002) 122-128
93. Lodder J., Raak van E., and Kessels F. Early GABA-ergic activation study in stroke. Abstract presented at the Ongoing Clinical Trials Session. 26th International Stroke Conference, Fort Lauderdale, FL, February (2001)
94. Hall E., Pazara K., and Braughler J. 21-aminosteroid lipid peroxidation inhibitor U74006F protects against cerebral ischemia in gerbils. Stroke 19 (1988) 997-1002
95. Zuccarello M., Marsch J., Schmitt G., Woodward J., and Anderson D. Effect of the 21-aminosteroid U-74006 on cerebra vasospasm following subarachnoid hemorrhage. J Neurosurg 71 (1989) 98-104
96. Hall E., Andrus P., Smith S., Oostveen J., Scherch H., Lutzke B., et al. Neuroprotective efficacy of microvascularly-localized versus brain-penetrating antioxidants. Acta Neurochir Suppl (Wien) 66 (1996) 107-113
97. The STIPAS Investigators. Safety study of tirilazad mesylate in patients with acute ischemia stroke (STIPAS). Stroke 25 (1994) 418-423
98. The RANTTAS Investigators. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). Stroke 27 (1996) 1453-1458
99. Haley E., and on behalf of the RANTTAS II Investigators. High-dose tirilazad for acute stroke (RANTTAS II). Stroke 29 (1998) 1256-1257
100. Tirilazad International Steering Committee. Tirilazad mesylate in acute ischemic stroke: a systematic review. Stroke 32 (2000) 2257-2265
101. Van der Worp H., Kappelle L., Algra A., Bar P., Orgogozo J., Ringelstein E., et al., on behalf of the TESS and TESS II Investigators. The effect of tirilazad mesylate on infarct volume of patients with acute ischemic stroke. Neurology 58 (2002) 133-135
102. Beck T., and Bielenberg G. Failure of the lipid peroxidation inhibitor U74006F to improve neurological outcome after transient forebrain ischemia in the rat. Brain Res 532 (1990) 336-338
103. Ichikawa S., Omura K., Katayama T., Okamura N., Ontsuka T., Ishibashi S., et al. Inhibition of superoxide anion production in guinea pig polymorphonuclear leudocytes by a seleno-organic compound, ebselen. J Pharmacobio-Dyn 10 (1987) 595-597
104. Hattori R., Inoue R., Sase K., Eizawa H., Kosuga K., Aoyama T., et al. Preferential inhibition of inducible nitric oxide synthase by ebselen. Eur J Pharmacol 267 (1994) R1-R2
105. Maiorino M., Roveri A., Coassin M., and Ursini F. Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51). Biochem Pharmacol 37 (1988) 2267-2271
106. Yamaguchi T., Sano K., Takakura K., Saito I., Shinohara Y., Asano T., et al., for the Ebselen Study Group. Ebselen in acute ischemic stroke: A placebo-controlled, double-blind clinical trial. Stroke 29 (1998) 12-17
107. Zhao Z., Cheng M., Maples K., Ma J., Buchan A., et al. NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat. Brain Res 909 (2001) 46-50
108. Sydserff S., Borelli A., Green A., and Cross A. Effect of NSY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat: Studies on dose, plasma concentration and therapeutic time window. Br J Pharmacol 135 (2002) 103-112
109. Marshall J., Duffin K., Green A., and Ridley R. NXY-059, a free radical-trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in a primate species. Stroke 32 (2001) 190-198
110. Cross A. The effect of increasing doses of NXY-059 on infarct size following permanent middle cerebral artery occlusion in the rat. AstraZeneca Report (2000)
111. Lees K., Sharma A., Barer D., Ford G., Kostulas V., Cheng Y., et al., for the SA-NXY-0003 Investigators. Tolerability and pharmacokinetics of the nitrone NXY-059 in patients with acute stroke. Stroke 32 (2001) 675-680
112. Okada Y., Copeland B., More E., Tung M., Thomas W., del Zoppo G., et al. P-selectin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 25 (1994) 202-211
113. Zhang R., Chopp M., Zaloga C., Zhang Z., Jiang N., Gautam S., et al. The temporal profiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat. Brain Res 682 (1995) 182-188
114. Soriano S., Coxon A., Wang Y., Frosch M., Lipton S., Hickey P., et al. Mice deficient in Mac-1(CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 30 (1999) 134-139
115. Kitagawa K., Matsumoto M., Mabuchi T., Yagita Y., Ohtsuki T., Hori M., et al. Deficiency of intercellular adhesion molecule-1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia. J Cereb Blood Flow Metab 18 (1998) 1336-1345
116. Clark W., Madden K., Rothlein R., and Zivin J. Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment. Stroke 22 (1991) 877-883
117. Zhang R., Chopp M., Jiang N., Tang W., Prostak J., Manning A., et al. Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 26 (1995) 1438-1442
118. Zhang R., Zhang Z., Chopp M., and Zivin J. Thrombolysis with tissue plasminogen activator alters adhesion molecule expression in the ischemic rat brain. Stroke 30 (1999) 624-629
119. Fassbender K., Mossner R., Motsch L., Kischka V., Garu A., and Hennerici M. Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke. Stroke 26 (1995) 1361-1364
120. Bitsch A., Klene W., Murtada L., Prange H., and Rieckmann P. A longitudinal prospective study of soluble adhesion molecules in acute stroke. Stroke 29 (1998) 2129-2135
121. Frijns C., Kappelle L., van Gijn J., Nieuwenhuis H., Sixma J., and Fijnheer R. Soluble adhesion molecules reflect endothelial cell activation in ischemic stroke and in carotid atherosclerosis. Stroke 28 (1997) 2214-2218
122. Lindsberg P., Carpen O., Paetau A., Karjalainen-Lindsberg M., and Kaste M. Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation 94 (1996) 939-945
123. Schneider D., Berrouschot J., Brandt T., Hacke W., Ferbert A., and Norris S. Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke. Eur Neurol 40 (1998) 78-83
124. Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 57 (2001) 1428-1434
125. Furuya K., Takeda H., Azhar S., McCarron R., Chen Y., Ruetzler C., et al. Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke 32 (2001) 2665-2674
126. Manabat C., Han B., Wendland M., Derugin N., Fox C., Choi J., et al. Reperfusion differentially induces caspases-3 activation in ischemic core and penumbra after stroke in immature brain. Stroke 34 (2003) 207-213
127. Robertson G., Crocker S., Nicholson D., and Schulz J. Neuroprotection by the inhibition of apoptosis. Brain Pathol 10 (2000) 283-292
128. Satoh S., Ikegaki I., Suzuki Y., Asano T., Shibuya M., and Hidaka H. Neuroprotective properties of a protein kinase inhibitor against ischaemia-induced neuronal damage in rats and gerbils. Br J Pharmacol 118 (1996) 1592-1596
129. Wang K., Nath R., Rosner A., Raser J., Buroker-Kilgore M., Hajimohammadreza I., et al. An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. Proc Natl Acad Sci USA 93 (1996) 6687-6692
130. Barone F., Irving E., Ray A., Lee J., Kassis S., Kumar S., et al. SB 239063, a second-generation p38 mitogen-activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia. J Pharmacol Exp Ther 296 (2001) 312-321
131. Markgraf C., Velayo N., Johnson M., McCarty D., Medhi S., Koehl J., et al. Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats. Stroke 29 (1998) 152-158
132. Yrjanheikki J., Keinanen R., Pellikka M., Hokfelt T., Koistinaho J., et al. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 95 (1998) 15769-15774
133. Yrjanheikki J., Tikka T., Keinanen R., Goldsteins G., Chan P., and Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 96 (1999) 13496-13500
134. Wang C., Yang T., Noor R., and Shuaib A. Delayed minocycline but not delayed mild hypothermia protects against embolic stroke. BMC Neurol 2 (2002) 2
135. Asai A., Qiu J., Narita Y., Chi S., Saito N., Shinoura N., et al. High level calcineurin activity predisposes neuronal cells to apoptosis. J Biol Chem 274 (1999) 34450-34458
136. Herr I., Martin-Villalba A., Kurz E., Roncaioli P., Schenkel J., Cifone M., et al. FK506 prevents stroke-induced generation of ceramide and apoptosis signaling. Brain Res 826 (1999) 210-219
137. Bochelen D., Rudin M., and Sauter A. Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal cerebral ischemic/reperfusion injury. J Pharmacol Exp Ther 288 (1999) 653-659
138. Ebisu T., Katsuta K., Fujikawa A., Aoki I., Vaneda M., Naruse S., et al. Early and delayed neuroprotective effects of FK506 on experimental focal ischemia quantitatively assessed by diffusion-weighted MRI. Magn Reson Imaging 19 (2001) 153-160
139. McCarter J., McGregor A., Jones P., and Sharkey J. FK506 protects brain tissue in animal models of stroke. Transplant Proc 33 (2001) 2390-2392
140. Arii T., Kamiya T., Arii K., Ueda M., Nito C., Katsura K., et al. Neuroprotective effect of immunosuppressant FK506 in transient focal ischemia in rat: Therapeutic time window for FK506 in transient focal ischemia. Neurol Res 23 (2001) 755-760
141. Takamatsu H., Tsukada H., Noda A., Kakiuchi T., Nishiyama S., Nishimura S., et al. FK506 attenuates early ischemic neuronal death in a monkey model of stroke. J Nucl Med 42 (2001) 1833-1840
142. Limbourg F., Huang Z., Plumier J., Simoncini T., Fujioka M., Tuckermann J., et al. Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J Clin Invest 110 (2002) 1729-1738
143. Mulley G., Wilcox R., and Mitchell J. Dexamethasone in acute stroke. BMJ 2 (1978) 994-996
144. Norris J., and Hachinski V. High dose steroid treatment in cerebral infarction. BMJ 292 (1986) 21-23
145. Qizilbash N., Lewington S., and Lopez-Arrieta J. Corticosteroids for acute ischaemic stroke. Cochrane Database Syst Rev (2000) CD000064-2
146. Vayssiere B., Dupont S., Choquart A., Petit F., Garcia T., Marchandeau C., et al. Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit anti-inflammatory activity in vivo. Mol Endocrinol 11 (1997) 1245-1255
147. Belayev L., Liu Y., Zhao W., Busto R., and Ginsburg M. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke 32 (2001) 553-560
148. Zoellner H., Hofler M., Beckmann R., Hufnagl P., Vanyek E., Bielek E., et al. Serum albumin is a specific inhibitor of apoptosis in human endothelial cells. J Cell Sci 109 (1996) 2571-2580
149. Rodriguez de Turco I., Belayev L., Liu Y., Busto R., Parkins N., Bazan N., et al. Systemic fatty acid responses to transient focal cerebral ischemia: influence of neuroprotectant therapy with human albumin. J Neurochem 83 (2002) 515-524
150. Lenzi G., Grigoletto F., Gent M., Roberts R., Walker M., Easton J., et al., the Early Stroke Trial Group. Early treatment of stroke with monosialoganglioside GM-1: Efficacy and safety results of the early stroke trial. Stroke 25 (1994) 1552-1558
151. Schwab M., Antonow-Schorke I., Zwiener U., and Bauer R. Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats. J Neural Transm Suppl 53 (1998) 299-311
152. Ladurner F. Neuroprotection in acute ischaemic stroke [abstract]. Stroke 32 (2001) 323
153. Rao A., Hatcher J., and Dempsey R. CDP-choline: neuroprotection in transient forebrain ischemia of gerbils. J Neurosci Res 58 (1999) 697-705
154. Adibhatla R., Hatcher J., and Dempsey R. Citicoline: neuroprotective mechanisms in cerebral ischemia. J Neurochem 80 (2002) 12-23
155. Krupinski J., Ferrer I., Barrachina M., Secades J., Mercadal J., Lozano R., et al. CDP-choline reduces procaspase and cleaved caspae-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 42 (2002) 846-854
156. Clark W., Warach S., and for the Citicholine Study Group. Randomized dose response trial of citicholine in acute ischemic stroke patients. Neurology 49 (1997) 671-678
157. Clark W., Williams B., Selzer K., et al., for the Citicoline Stroke Study Group. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 30 (1999) 2592-2597
158. Clark W., Wechsler L., Sabounjian L., Schwiderski U., and for the Citicoline Stroke Study Group. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 57 (2001) 1595-1602
159. Warach S., Pettigrew L., Dashe J., Pullicino P., Lefkowitz D., Sabounjian L., et al. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol 48 (2000) 713-722
160. Corso A., Arena M., Ventimiglia A., Bizzarro G., Campo G., and Rodolico F. CDP-choline for cerebrovascular disorders: Clinical evaluation and evaluation of electrophysiological symptomology. Clin Ter 102 (1982) 379-386
161. Tazaki Y., Sakai F., Otomo E., Kutsuzawa T., Kameyama M., Omae T., et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 19 (1988) 211-216
162. Saver J., and Wilterdink J. Choline precursors in acute and subacute stroke: a meta-analysis. Stroke 33 (2002) 353
163. Davalos A., Castillo J., Alvarez-Sabin J., Secades J., Mercadal J., Lopez S., et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke 33 (2002) 2850-2857
164. Andersen M., Overgaard K., Meden P., and Boysen G. Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model. Stroke 30 (1999) 1464-1471
165. Siren A., and Ehrenreich H. Erythropoietin-a novel concept for neuroprotection. Eur Arch Psychiatry Clin Neurosci 251 (2001) 179-184
166. Sakanaka M., Wen T., Matsuda S., Morishita E., Nagao M., et al. In vitro evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA 95 (1998) 4635-4640
167. Morishita E., Masuda S., Nagao M., Yasuda Y., and Sasaki R. Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76 (1997) 105-116
168. Brines M., Ghezzi P., Keenan S., Angello D., de Lanerolle M., Cerami C., et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 97 (2000) 10526-10531
169. Siren A., Fratelli M., Brines M., et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 98 (2000) 4044-4049
170. Ay I., Sugimori H., and Finklestein S. Intravenous basic fibroblast growth factor (bFGF) decreases DNA fragmentation and prevents downregulation of Bcl-2 expression in the ischemic brain following middle cerebral artery occlusion in rats. Mol Brain Res 87 (2001) 71-80
171. Kawamata T., Kietrich W., Schallert T., Gotts J., Cocke R., Benowitz L., et al. Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction. Proc Natl Acad Sci USA 94 (1997) 8179-8184
172. Li Q., and Stephenson D. Postischemic administration of basic fibroblast growth factor improves sensorimotor function and reduces infarct size following permanent focal cerebral ischemia in the rat. Exp Neurol 177 (2002) 531-537
173. Schabitz W., Li F., Irie K., Sandage Jr. B., Locke K., Fisher M., et al. Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia. Stroke 30 (1999) 427-431
174. Ma J., Aui J., Hirt L., Dalkara T., and Moskowitz M. Synergistic protective effect of caspases inhibitors and bFGF against brain injury induced by transient focal ischaemia. Br J Pharmacol 133 (2001) 345-350
175. Bogousslavsky J., Victor S., Salinas E., Pallay A., Ponnan G., Fieschi C., et al., for the European-Australian Fiblast in Acute Stroke Group. Fiblast (trafermin) in acute stroke: results of the Eur-Australian phase II/III safety and efficacy trial. Cerebrovasc Dis 14 (2002) 239-251
176. Song B., Vinters H., Wu D., and Pardridge W. Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. J Pharmacol Exp Ther 301 (2002) 605-610
177. Krupinski J., Issa R., Bujny T., Slevin M., Kumar P., Kamar S., et al. A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans. Stroke 28 (1997) 564-573
178. Semkova I., and Krieglstein J. Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res Rev 30 (1999) 176-188
179. Wang Y., Chang C., Morales M., Chang Y., and Hoffer J. Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury. Ann N Y Acad Sci 962 (2002) 423-437
180. Kilic E., Dietz G., Hermann D., and Bahr M. Intravenous TAT-Bcl-XL is protective after middle cerebral artery occlusion in mice. Ann Neurol 52 (2002) 617-622
181. Busto R., Dietrich W., Globus M., Valdes I., Scheinberg P., and Ginsberg M. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7 (1987) 729-738
182. Buchan A., and Pulsinell W. Hypothermia but not N-methyl-d-aspartate antagonist MK-801 attenuates neuronal damage in gerbils subjected to transient global ischemia. J Neurosci 10 (1990) 311-316
183. Minamisawa H., Nordstrom C., Smith M., and Siesjo B. The influence of mild body and brain hypothermia on ischemic brain damage. J Cereb Blood Flow Metab 10 (1990) 365-374
184. Coimbra C., and Wielock T. Hypothermia ameliorates neuronal survival when induced 2 hours after ischemia in the rat. Acta Physiol Scand 146 (1992) 543-544
185. Meden P., Overguard K., Pedersen H., and Boysen G. The influence of body temperature on infarct volume and thrombolytic therapy in a rat embolic stroke model. Brain Res 647 (1994) 131-138
186. Corbett D., Nurse S., and Colbourne F. Hypothermic neuroprotection: a global ischemia study using 18- to 20-month-old gerbils. Stroke 28 (1997) 2238-2242
187. Barone F., Feuerstein G., and White R. Brain cooling during transient focal ischemia provides complete neuroprotection. Neurosci Biobehav Rev 21 (1997) 31-44
188. Maier C., Ahern K., Cheng M., Lee J., Yenari M., Steinberg G., et al. Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: Effects of neurologic outcome, infarct size, apoptosis, and inflammation. Stroke 29 (1998) 2171-2180
189. Corbett D., Hamilton M., and Colbourne F. Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion. Exp Neurol 163 (2000) 200-206
190. Kawai N., Okauchi M., Morisaki K., and Nagao S. Effects of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia in rats. Stroke 31 (2000) 1982-1989
191. Nakashima K., and Todd M. Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke 27 (1996) 913-918
192. Koizumi H., Fujisawa H., Ito H., Maekawa T., Pi X., and Bullock R. Effects of mild hypothermia on cerebral blood flow-independent changes in cortical extracellular levels of amino acids following contusion trauma in the rat. Brain Res 747 (1997) 304-312
193. Sick T., Xu G., and Perez-Pinzon A. Mild hypothermia improves recovery of cortical extracellular potassium ion activity and excitability after middle cerebral artery occlusion in the rat. Stroke 30 (1999) 2416-2421
194. Prakasa Babu P., Yoshida Y., Su M., Segura M., Kawamura S., Yasui N., et al. Immunohistochemical expression of Bcl-2, Bax and cytochrome c following focal cerebral ischemia and effect of hypothermia in rat. Neurosci Lett 291 (2000) 196-200
195. Ishikawa M., Sekizuka E., Sato S., Yamaguchi N., Inamasu J., Bertalanffy H., et al. Effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion. Stroke 30 (1999) 1679-1686
196. Inamasu J., Suga S., Sato S., Horiguchi T., Akaji K., Mayanogi K., et al. Post-ischemic hypothermia delayed neutrophil accumulation and microglial activation following transient focal cerebral ischemia in rats. J Neuroimmunol 109 (2000) 66-74
197. Zeiner A., Holzer M., Sterz F., Behringer W., Schorkuber W., Mullner M., et al. for the Hypothermia After Cardiac Arrest (HACA) Study Group. Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. Stroke 31 (2000) 86-94
198. Felberg R., Krieger D., Chuang R., Persse P., Burgin W., Hickenbottom S., et al. Hypothermia after cardiac arrest: feasibility and safety of an external cooling protocol. Circulation 104 (2001) 1799-1804
199. Bernard S., Gray T., Buist M., Jones B., Silvester W., Gutteridge G., et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346 (2002) 557-563
200. The Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346 (2002) 549-556
201. Colbourne F., Li H., and Buchan A. Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. J Cereb Blood Flow Metab 19 (1999) 742-749
202. Azzimondi G., Bassein L., Nonino F., Fiorani L., Vignatelli L., Re G., et al. Fever in acute stroke worsens prognosis. Stroke 26 (1995) 2040-2043
203. Jorgensen H., Reith J., Pedersen P., Nakayama H., and Olsen T. Body temperature and outcome in stroke patients [letter]. Lancet 348 (1996) 193
204. Reith J., Jorgensen H., Pedersen P., Nakayama H., Raaschou H., Jeppesen L., et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet 347 (1996) 422-425
205. Wang Y., Lim L., Levi C., Heller R., and Fischer J. Influence of admission body temperature on stroke mortality. Stroke 31 (2000) 404-409
206. Schwab S., Schwarz S., Spranger M., Keller E., Bertram M., and Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 29 (1998) 2461-2466
207. Kammersgaard L., Rasmussen B., Jorgensen H., Reith J., Weber U., and Olsen T. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: a case-control study. Stroke 31 (2000) 2251-2256
208. Schwab S., Georgiadis D., Berrouschot J., Schellinger P., Graffagnino C., and Mayer S. Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 32 (2001) 2033-2035
209. Steiner T., Friede T., Aschoff A., Schellinger P., Schwab S., and Hacke W. Effect and feasibility of controlled rewarming after moderate hypothermia in stroke patients with malignant infarction of the middle cerebral artery. Stroke 32 (2001) 2833-2835
210. Kreiger D., DeGeorgia M., Abou-Chebl A., Andrefsky J., Sila C., Katzan I., et al. Cooling for Acute Ischemic Brain Damage (COOL AID): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 32 (2001) 1847-1854
211. Georgiadis D., Schwarz S., Kollmar R., and Schwab S. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke 32 (2001) 2550-2553
212. Strong R., Grotta J., and Aronowski J. Combination of low dose ethanol and caffeine protects brain from damage produced by focal ischemia in rats. Neuropharmacology 39 (2000) 515-522
213. Aronowski J., Strong R., Shirzadi A., and Grotta J. Ethanol plus caffeine (caffeinol) for treatment of ischemic stroke: preclinical experience. Stroke 34 (2003) 1246-1251
214. Piriyawat P., Labiche L., Burgin W., Aronowski J., and Grotta J. Pilot dose-escalation study of caffeine plus ethanol (Caffeinol) in acute ischemic stroke. Stroke 34 (2003) 1242-1245
215. Bowes M., Burhop K., and Zivin J. Diaspirin cross-linked hemoglobin improves neurological outcome following reversible but not irreversible CNS ischemia in rabbits. Stroke 25 (1994) 2253-2257
216. Cole D., Schell R., Przybelski R., Drummond J., and Bradley K. Focal cerebral ischemia in rats: effect of hemodilution with cross-linked hemoglobin on CBF. J Cereb Blood Flow Metab 12 (1992) 971-976
217. Cole D., Schell R., Drummond J., and Reynolds L. Focal cerebral ischemia in rats: effect of hypervolemic hemodilution with diaspirin crossed-linked hemoglobin versus albumin on brain injury and edema. Anesthesiology 78 (1993) 335-342
218. Grotta J., and Aronowski J. DCLHb for focal ischemia and reperfusion. Cerebrovasc Dis 6 (1996) 189
219. Saxena R., Wijnhoud A., Carton H., Hacke W., Kaste M., Przybelski R., et al. Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke 30 (1999) 993-996
220. Singhal A., Dijkhuizen R., Rosen B., and Lo E. Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke. Neurology 58 (2002) 945-952
221. Atochin D., Fisher D., Demchenko I., and Thom S. Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion. Undersea Hyperb Med 27 (2000) 185-190
222. Badr A., Yin W., Mychaskiw G., and Zhang J. Effect of hyperbaric oxygen on striatal metabolites: A microdialysis study in awake freely moving rats after MCA occlusion. Brain Res 916 (2001) 85-90
223. Burt J., Kapp J., and Smith R. Hyperbaric oxygen and cerebral infarction in the gerbil. Surg Neurol 28 (1987) 265-268
224. Weinstein P., Anderson G., and Telles D. Results of hyperbaric oxygen therapy during temporary middle cerebral artery occlusion in unanesthetized cats. Neurosurg 20 (1987) 518-524
225. Veltkamp R., Warner D., Domoki F., Brinkhous A., Toole J., and Busija D. Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats. Brain Res 853 (2000) 68-73
226. Chang C., Niu K., Hoffer B., Wang Y., and Borlongan C. Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Exp Neurol 166 (2000) 298-306
227. Sunami K., Takeda Y., Hashimoto M., and Hirakawa M. Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery. Crit Care Med 28 (2000) 2831-2836
228. Jacobson I., and Lawson D. The effect of hyperbaric oxygen on experimental cerebral infarction in the dog. J Neurosurg 20 (1963) 849-859
229. Roos J., and Jackson-Friedman L.P. Effects of hyperbaric oxygen on neurologic outcome for cerebral ischemia in rats. Acad Emerg Med 5 (1998) 18-24
230. Hjelde A., Hjelstuen M., Haraldseth O., Martin D., Thom R., and Brubakk O. Hyperbaric oxygen and neutrophil accumulation/tissue damage during permanent focal cerebral ischaemia in rats. Eur J Appl Physiol 86 (2002) 401-405
231. Anderson D., Bottini A., Jagiella W., Westphal B., Ford S., Rockswold G., et al. A pilot study of hyperbaric oxygen in the treatment of human stroke. Stroke 22 (1991) 1137-1142
232. Nighoghossian N., Trouillas P., Adeleine P., and Salord F. Hyperbaric oxygen in the treatment of acute ischemic stroke: a double-blind pilot study. Stroke 26 (1995) 1369-1372