Neuroprotection in acute ischaemic stroke. II: Clinical potential

Vascular Medicine

Volumn 4, Issue 3, 1999, Pages 149-163

  Davis, Michelle ^a   Barer, David ^a  

^a QUEEN ELIZABETH HOSPITAL   (United Kingdom)

Author keywords

Acute stroke treatment; Brain blood flow; Brain ischaemia; Brain protection; Cerebral infarction; Cerebral ischaemia; Clinical trials; Glutamate antagonists; Ischaemic cascade; Ischaemic penumbra; N methyl D aspartate; Neuronal injury

Indexed keywords

4 AMINOBUTYRIC ACID; ALTEPLASE; AMINOGUANIDINE; AMPA RECEPTOR ANTAGONIST; ANESTHETIC AGENT; ANTICOAGULANT AGENT; ANTIOXIDANT; ARGININE; CALCIUM CHANNEL BLOCKING AGENT; GLUTAMATE RECEPTOR ANTAGONIST; NEUROPROTECTIVE AGENT; NITRIC OXIDE SYNTHASE INHIBITOR; PHENYTOIN; THEOPHYLLINE; VASODILATOR AGENT;

BRAIN INFARCTION; BRAIN PERFUSION; CEREBROVASCULAR ACCIDENT; CLINICAL PRACTICE; CLINICAL TRIAL; DRUG EFFICACY; HUMAN; MALE; META ANALYSIS; NEUROPROTECTION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; TREATMENT PLANNING;

EID: 0032837864     PISSN: 1358863X     EISSN: None     Source Type: Journal    
DOI: 10.1177/1358836x9900400306     Document Type: Review

References (195)

1. Davis M, Barer D. Theoretical aspects of neuroprotection in acute ischaemic stroke. 1: basic mechanisms. Vasc Med Rev 1995; 6: 283-98.
2. Del Zoppo GJ. Why do all drugs work in animals but none in stroke patients? 1. Drugs promoting cerebral blood How. J Intern Med 1995; 237: 79-88.
3. Grotta J. Why do all drugs work in animals but none in stroke patients? 2. Neuroprotective therapy. J Intern Med 1995; 237: 89-94.
4. Sandercock P, Willems H. Medical treatment of acute ischaemic stroke. Lancet 1992; 339: 537-39.
5. Del Zoppo GJ. Acute stroke: on the threshold of a therapy? N Engl J Med 1995; 333: 1632-33.
6. Moskowitz MA, Dalkara T. Opportunities for collective wisdom in stroke research. Cerebrovasc Dis 1997; 7: 313-14.
7. Hossman K-A. What can we learn from experimental ischaemia research? Cerebrovasc Dis 1997; 7: 315-17.
8. Davis M, Mendelow AD, Perry RH. Chambers IR. James OF. Experimental stroke and neuroprotection in the aging rat brain. Stroke 1995; 26: 1072-78.
9. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997; 349: 1569-81.
10. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised, placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997; 349: 1641-49.
11. Garcia JH, Liu KF, Ho KL. Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 1995; 26: 636-43.
12. Garcia JH, Wagner S, Liu KF, Hu XJ. Mohr JP. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats: statistical validation. Stroke 1995; 26: 627-35.
13. Hossmann KA. Viability thresholds and the penumbra of focal ischemia. Ann Neurol 1994; 36: 557-65.
14. Wise RJS, Bernardi S, Frackowiak RSJ, Legg NJ, Jones T. Serial observations on the pathophysiology of acute stroke. Brain 1983; 106: 197-222.
15. Higano S, Uemura K, Shishido F, Kanno I, Tomura N, Sakamoto K. Evaluation of critically perfused area in acute ischémic stroke for therapeutic reperfusion: a clinical PET study. Ann Nucl Med 1993; 7: 167-71.
16. Marchal G, Serrati C, Rioux P et al. PET imaging of cerebral perfusion and oxygen consumption in acute ischaemic stroke: relation to outcome. Lancet 1993; 341: 925-27.
17. Marchal G, Rioux P, Serrati C et al. Value of acute stage positron emission tomography in predicting neurological outcome after ischemic stroke: further assessment. Stroke 1995; 26: 524-25.
18. Minematsu K, Yamaguchi T, Omae T. Spectacular shrinking deficit. Neurology 1992; 42: 157-62.
19. Marchal G, Beaudouin V, Rioux P et al. Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. Stroke 1996; 27: 599-606.
20. Welch KM, Windham J, Knight RA et al. A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging. Stroke 1995; 26: 1983-89.
21. Warach S, Dashe JF, Edelman RR. Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging: a preliminary analysis. J Cereb Blood Flow Metab 1996; 16: 53-59.
22. Moseley ME, Cohen Y, Mintorovitch J et al. Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med 1990; 14: 330-46.
23. Heiss WD, Graf R, Fujita T et al. Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats. Stroke 1997; 28: 2045-51.
24. Heiss WD, Grond M, Thiel A et al. Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke. Stroke 1998; 29: 454-61.
25. Ramsay SC, Weiller C, Myers R et al. Monitoring by PET of macro-phage accumulation in brain after ischemic stroke. Lancet 1992; 339: 1054-55.
26. Bullock R, Zauner A, Woodward J, Young HF. Massive persistent release of excitatory amino acids following human occlusive stroke. Stroke 1995; 26: 2187-89.
27. Fieschi C, Argentino C, Lenzi G et al. Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours. J Neurol Sci 1989; 91: 311-22.
28. Furlan M, Marchal G, Viader F, Derlon JM, Baron JC. Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra. Ann Neurol 1996; 40(2): 216-26.
29. Baird AE, Donnan GA. Prognostic value of reperfusion during first 48 hours of ischaemic stroke. Lancet 1993; 342: 236.
30. Zanette EM, Roberti C, Mancici G, Pozzilli C, Bragoni M, Toni D. Spontaneous middle cerebral artery reperfusion in ischemic stroke: a follow-up study with transcranial Doppler. Stroke 1995; 26: 430-33.
31. Feinberg W, Bruck D, Ring M, Corrigan J. Hemostatic markers in acute stroke. Stroke 1989; 20: 592-97.
32. Tohgi H, Kaurashima M, Tamura K, Suzuki H. Coagulation-fibrinolysis abnormalities in acute and chronic phases of cerebral thrombosis and embolism. Stroke 1990; 21: 1663-67.
33. Jones HR, Millikan CH. Temporal profile (clinical course) of acute carotid system cerebral infarction. Stroke 1976; 7: 64-71.
34. Hachinski V, Norris J. The deteriorating stroke. In: Hachinski V, Norris J (eds). The acute stroke. Philadelphia: FA Davies, 1985: 123-10.
35. Britton MD. Roden A. Progression of stroke after arrival at hospital. Stroke 1985; 16: 629-32.
36. Davalos A, Cendra E, Teruel J, Martinez M, Genis D. Deteriorating ischemic stroke: risk factors and prognosis. Neurology 1990; 40: 1865-69.
37. Toni D, Riorelli M, Gentile M et al. Progressing neurological deficit secondary to acute ischemic stroke. Arch Neurol 1995; 52: 670-75.
38. Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Effect of blood pressure and diabetes on stroke in progression. Lancet 1994; 344: 156-59.
39. Strandgaard S, Paulson OB. Cerebral autoregulation. Stroke 1984; 15: 413-11.
40. Dirnagel U. Pulsinelli W. Autoregulation of cerebral blood flow in experimental focal brain ischemia. J Cereb Blood Flow Metab 1990; 10: 327-36.
41. Robinson T, Waddington A, Ward-Close S, Taub N, Potter J. The predictive role of 24-hour compared to casual blood pressure levels on outcome following acute stroke. Cerebrovasc Dis 1997; 7: 264-72.
42. Lisk DR, Grotta JC, Lamki LM et al. Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. Arch Neurol 1993; 50: 855-62.
43. Wahlgren NG, Macmahon DG, Dekeyser J, Indredavik B, Ryman T. Intravenous Nimodipine West-European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischemic stroke. Cerebrovasc Dis 1994; 4: 204-10.
44. O'Connell JE, Gray CS. Treating hypertension after stroke. BMJ 1994; 308: 1523-24.
45. Bath F, Bath P. Blood pressure management in acute stroke. In: Warlow C, van Gijn J, Sandercock P (eds). Stroke module of the Cochrane database of systematic reviews. The Cochrane Collaboration; Issue 3. Oxford: Update Software, 1997.
46. Asplund K. Any progress on progressing stroke? Cerebrovasc Dis 1992; 2: 317-19.
47. Weir CJ, Murray GD, Dyker AG, Lees KR. Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study. BMJ 1997; 314: 1303-306.
48. Reith J, Jorgensen HS, Pedersen PM et al. Body temperature in acute stroke: relation to stroke seventy, infarct size, mortality and outcome. Lancet 1996; 347: 422-25.
49. Davalos A, Castillo J, Pumar JM, Noya M. Body temperature and fibrinogen are related to early neurological deterioration in acute ischaemic stroke. Cerebrorasc Dis 1997; 7: 64-69.
50. Langhorne P, Williams BO, Gilchrist W, Howie K. Do stroke units save lives? Lancet 1993; 342: 395-98.
51. Stroke Unit Triallists' Collaboration. collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. BMJ 1997; 314: 1151-59.
52. Marcoux FW, Morawetz RB, Gowell RM et al. Differential regional vulnerability in transient focal cerebral ischaemia. Stroke 1982; 13: 339-46.
53. Weinstein PR, Anderson GG, Telles DA. Neurological deficit and cerebral infarction after temporary middle cerebral artery occlusion in unanaesthetised cats. Stroke 1986; 17: 318-24.
54. Memezawa H, Smith ML, Siesjo BK. Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke 1992; 23: 552-59.
55. Ho U, Ohno K, Nakamura R et al. Brain oedema during ischemia and after restoration of blood flow. Measurement of hydrogen peroxide, sodium, potassium content and plasma protein permeability. Stroke 1979; 10: 542-47.
56. McCord JM. Oxygen derived free radicals in post ischemic tissue injury. N Engl J Med 1985; 312: 159-63.
57. Kontos HA. Oxygen radicals in cerebral vascular injury. Circ Res 1985; 57: 508-16.
58. Siesjo BK, Agardh CD, Bengtsson F. Free radicals and brain damage. Cerebrovasc Brain Metab Rev 1989; 1: 165-211.
59. Yang GY, Betz, AL, Hsu CY. Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats. Stroke 1994; 25: 1658-65.
60. Wardlaw JM, Warlow CP. Thrombolysis in acute ischaemic stroke -does it work? Stroke 1992; 23: 1826-39.
61. ISIS-2 Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17, 187 cases of suspected acute myocardial infarction. ISIS-2. Lancet 1988; ii: 349-60.
62. Hass WK, Easton JD, Adams HP Jr et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med 1989; 321: 501-507.
63. CAPRIE Study Group (Gent M, Beaumont D, Blanchard J et al). A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329-39.
64. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143: 1-13.
65. Verheugt FWA. In search of a superaspirin for the heart. Lancet 1997; 349: 1409-10.
66. Sandercock PAG, van den Belt AGM, Lindley RI, Slattery J. Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials. J Neurol Neurosurg Psychiatry 1993; 56: 17-25.
67. Kay R, Ka Sing Wong, Yuk Ling Yu et al. Low molecular weight heparin for the treatment of acute ischaemic stroke. N Engl J Med 1995; 333: 1588-93.
68. Counsell C, Sandercock P. The use of low-molecular-weight heparins or heparinoids compared to standard unfractionated heparin in acute ischaemic stroke. In: Warlow C, van Gijn J, Sandercock P (eds). Stroke module of the Cochrane database of systematic reviews. The Cochrane Collaboration: Issue 2. Oxford: Update Software, 1997.
69. Duke RJ, Bloch RF, Turpie AGG, Trebilcock R, Bayer N. Intravenous heparin for the prevention of stroke progression in acute partial stable stroke: a randomized controlled trial. Ann Intern Med 1986; 105: 825-28.
70. Liu M, Counsell C, Wardlaw J. Fibrinogen depleting agents in acute ischaemic stroke. In: Warlow C, van Gijn J, Sandercock P (eds). Stroke module of the Cochrane database of systematic reviews. The Cochrane Collaboration; Issue 2. Oxford: Update Software, 1997.
71. Horowitz SH, Zito JL, Donnarumma RN, Patel M, Alvir J. Computed tomographic-angiographic findings within the first five hours of cerebral infarction. Stroke 1991; 22: 1245-53.
72. Meyer JS, Gilroy J, Barnhardt M. Therapeutic thrombolysis in cerebral thromboembolism. In: Millikan CH, Siekert RG, Whisnant JP eds. Cerebrovascular diseases: 4th Princeton Conference. New York: Grune & Stratton, 1965: 200-13.
73. Fletcher AP, Alkjaersig N, Lewis M et al. A pilot study of urokinase in cerebral infarction. Stroke 1976; 7: 135-42.
74. Del Zoppo GJ. Thrombolytic therapy in cerebrovascular disease. Stroke 1988; 19: 1174-79.
75. Levine SR, Brott TG. Thrombolytic therapy in cerebrovascular disorders. Prog Cardiovasc Dis 1992; 34: 235-62.
76. Von Kummer R, Holle R, Rosin L, Forsting M, Hacke W. Does arterial recanalisation improve outcome in carotid territory stroke? Stroke 1995; 26: 581-87.
77. Wardlow JM, Warlow CP. Thrombolysis in actute ischaemic stroke. Does it work? Stroke 1992; 23: 1826-39.
78. Donnan GA, Hommel M, Davis SM, Mcneil JJ. Streptokinase in acute ischaemic stroke. Steering Committees of the ASK and MAST-E trials. Lancet 1995; 346: 56.
79. Multicentre Acute Stroke Trial - Italy (MAST-I) Group. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet 1995; 346: 1509-14.
80. Hacke W, Kaste M, Fieschi C et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274: (13): 1017-25.
81. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581-87.
82. Moncada S. Biology and therapeutic potential of prostacyclin. Stroke 1983; 14: 157-68.
83. Bath P, Bath F. Prostacyclin and analogues in acute ischaemic stroke. In: Warlow C, van Gijn J, Sandercock P (eds). Stroke module of the Cochrane database of systematic reviews. The Cochrane Collaboration: Issue 2. Oxford: Update Softward, 1997.
84. Gottstein U, Paulson OB. The effect of intracarotid aminophylline infusion on the cerebral circulation. Stroke 1972; 3: 560-65.
85. Skinhoj E. Paulson OB. The mechanism of action of aminophylline upon cerebral vascular disorders. Acta Neurol Scand 1970; 46: 129-40.
86. Olivarius B de Fine. The actions of aminophylline in cerebral infarction and its relation to early assessment of immediate prognosis. Acta Neurol Scand 1970; 43 (suppl): 249-50.
87. Geismar P, Marquardsen J, Silvest J. Controlled trial of intravenous aminophylline in acute cerebral infarction. Acta Neurol Scand 1976; 54: 173-80.
88. Britton B, Faire U, Helmers C, Miah K, Rane A. Lack of effect of theophylline on the outcome of acute cerebral infarction. Acta Neurol Scand 1980; 62: 116-23.
89. Hayashi S, Nehls DG, Kieck CF, Vielma J, de Girolami U, Crowell RM. Beneficial effects of induced hypertension on experimental stroke in awake monkeys. J Neurosurg 1984; 60: 151-57.
90. Drummond JC, Itoh YS, Cole DJ, Shapiro HM. Phenylephrine-induced hypertension reduces ischemia following middle cerebral artery occlusion in rats. Stroke 1989; 20: 1538-44.
91. Asplund K. Hemodilution in acute stroke. Cerebrovasc Dis 1991; 1 (suppl 1): 129-38.
92. Thomas DJ, du Boulay GH, Marshall J et al. Effect of haematocrit on cerebral blood flow in man. Lancet 1977; ii: 941-43.
93. Brown MM, Marshall J. Regulation of cerebral blood flow in response to changes in blood viscosity. Lancet 1985; ii: 604-609.
94. Sunder-Plassman L, Klovekorn WP, Messmer K. Hemodynamic and rheological changes induced by hemodilution with colloids. In: Messmer K, Smith-Schonbein H (eds). Hemodilution: theoretical basis and clinical application. Basel: Karger, 1972: 184-202.
95. Chien S. Haemorheology in disease: pathophysiological significance and therapeutic implications. Clin Hemorheol 1981; 1: 419-42.
96. Asplund K, Israelsson K, Schampi I. Haemodilution in acute ischaemic stroke. In: Warlow C, van Gijn J, Sundercock P (eds). Stroke module of the Cochrane databse of systematic reviews. The Cochrane Collaboration; Issue 2. Oxford: Update Software, 1997.
97. Fazekas F, Aichner, Brainin M, Mamoli B, Zeiler K, for the MAHST Study Group. Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial. Cerebrovasc Dis 1997; 7 (suppl 4): 20.
98. The Hemodilution in Stroke Study Group. Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. Stroke 1989; 20: 317-23.
99. Goslinga H, Eijzenbach V, Heuvelmans JHA et al. Custom-tailored hemodilution with albumin and crystalloids in acute ischemic stroke. Stroke 1992; 23: 181-88.
100. Keipert PE, Adeniran AJ, Kwong S, Beneseh RE. Functional properties of a new cross-linked hemoglobin designed for use as a red cell substitute. Transfusion 1989; 29: 768-73.
101. Snyder SR, Welly EV, Walder RY, Williams LA et al. HbXL99a, a hemoglobin derivative that is cross-linked between the a subunits, is useful as a blood substitute. Proc Natl Acatl Sci USA 1987; 84: 7280-84.
102. Vandergriff KD, Medina F, Marini MA, Winslow RM. Equilibrium oxygen binding to human hemoglobin cross-linked between the a chains by Bis(3.5-dibromosalicyl) fumarate. J Biol Chem 1989; 264: 17824-33.
103. Cole DJ, Schell RM, Drummond JC, Reynolds L. Focal cerebral ischemia in rats: effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edeme. Anaesthesiology 1993; 78: 335-42.
104. Bowes MP, Burhop KE, Zivin JA. Diaspirin cross-linked hemoglobin improves neurological outcome following reversible but not irreversible CNS ischemia in rabbits. Stroke 1994; 25: 2253-57.
105. Hamilton PB, Miller A, van Slyjke DD. Renal effects of hemoglobin infusions in dogs in hemorrhagic shock. J Exp Med 1947; 86: 477-87.
106. Savitsky JP, Doczi J, Blacxk J, Arnold JD. A clinical safety trial of stroma-free hemoglobin. Clin Pharmacol Ther 1978; 23: 73-80.
107. Burhop KE, Farrell L, Nigro C, Tan D, Estep T. Effects of intravenous infusions of diaspirin cross-linked hemoglobin (DCLHb) on sheep. Biomater Artif Cells Immobilization Bioteclmol 1992; 20: 581-85.
108. Inoue Y, Takemoto K, Miyamoto T et al. Sequential CT scans in acute cerebral infarction. Radiology 1980; 135: 655-62.
109. Qizilbash N, Murphy M. Meta-analysis of trials of corticosteroids in acute stroke. Age Ageing 1993; 22 (suppl 2): 4.
110. Cantore G, Guidetti B, Virno M. Oral glycerol for the reduction of intracranial pressure. J Neurosurg 1964; 21: 278-83.
111. Meyer JS, Fununchi Y, Shimazu K, Okuchi I, Ericsson HD. Effect of intravenous infusion of glycerol on hemispheric blood flow and metabolism in patients with acute cerebral infarction. Stroke 1972; 3: 168-80.
112. a′ Rogvi-Hansen B, Boysen G. Glycerol treatment in acute ischaemic stroke. In: Warlow C, van Gijn J, Sandercock P (eds). Stroke module of the Cochrane database of systematic reviews. The Cochrane Collaboration; Issue 2. Oxford: Update Software, 1997.
113. Globus M-YT, Busto R, Dietrich WD, Martinez E, Valdes I, Ginsberg MD. Intra-ischemic extracellular release of dopamine and glutamate is associated with striatal vulnerability to ischemia. Neurosci Lett 1988; 91: 36-40.
114. Moyer DT, Welsh FA, Zager EL. Spontaneous cerebral hypothermia diminishes focal infarction in rat brain. Stroke 1992; 23: 1812-16.
115. Baker CJ, Onesti ST, Solomon RA. Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat; a time course study. J Neurosurg 1992; 77: 438-44.
116. Hoff EC, Yahn C. The effect of sodium 5,5-diphenylhydantoin upon the tolerance of rats and mice to decompression. Am J Physiol 1944; 141: 7-16.
117. Artru AA, Michenfelder JD. Cerebral protective, metabolic and vascular effects of phenytoin. Stroke 1980; 11: 377-82.
118. Hoff JT, Nishimura M, Newhfield P. Pentobarbital protection from cerebral infarction without suppression of edema. Stroke 1982; 13: 623-62.
119. Pickard JD, Murray GD, Illingworth R et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989; 298: 636-42.
120. Di Mascio R, Marchioli R, Tognoni G. From pharmacological promises to controlled clinical trials to meta-analysis and back: the case of nimodipine in cerebrovascular disorders. Clin Trials Meta-anal 1994; 29: 57-79.
121. Mohr JP, Orgogozo JM, Harrison MJG et al. Meta-analysis of oral nimodipine trials in acute ischaemic stroke. Cerebrovasc Dis 1994; 4: 197-203.
122. Limburg M. Very early nimodipine use in stroke - the first 100 patients - co-operation between GPs and neurologists. Stroke 1996; 27: 172.
123. Squire IB, Lees KR, Pryse-Phillips W et al. The effects of lifarizine in acute cerebral infarction - a pilot safety study. Cerebrovasc Dis 1996; 6: 156-60.
124. Benveniste H, Drejer J, Schousboe A, Diemer NH. Evaluation of the extracellular concentration of glutamate and aspartate in rat hippocampus during transient cerebral ischaemia monitored by intracerebral microdyalysis. J Neurochem 1984; 43: 1369-74.
125. Choi DW. Excitotoxicity. In: Meldrum BS (ed). Excitatory amino acid antagonists. Oxford: Blackwell Scientific Publications, 1991: 216-36.
126. Castillo J, Davalos A, Noya M. Progression of ischaemic stroke and excitotoxic aminoacids. Lancet 1997; 349: 79-83.
127. Bullock R. Strategies for neuroprotection with glutamate 129 antagonists. Extrapolating from evidence taken from the first stroke and head injury studies. Ann NY Acad Sci 1995; 765: 272-78.
128. Davis SM, Albers GW, Diener HC, Lees KR, Norris J. Termination of acute stroke studies involving Selfotel treatment. ASSIST Steering Committee. Lancet 1997; 349: 32.
129. McIntosh TK, Vink R, Weiner M, Faden AI. Alterations in free magnesium, high energy phosphates and lactate following traumatic brain injury: assessment by nuclear magnetic resonance spectroscopy. J Cereb Blood Flow Metab 1987; 7: (suppl 1): S620.
130. Izumi Y, Roussel S, Pinard E, Seylaz J. Reduction of infarct volume by magnesium after middle cerebral-artery occlusion in rats. J Cereb Blood Flow Metab 1991; 6: 1025-30.
131. Davis M, Perry RH, Mendelow AD. The effect of non-competitive N-methyl-D-aspartate receptor antagonism on cerebral oedema and cerebral infarct size in the aging ischaemic brain. Acta Neurochir 1997; 70 (suppl): 30-33.
132. Muir KW, Lees KR. A randomized, double-blind, placebo controlled pilot trial of intravenous magnesium sulfate in acute stroke. Stroke 1995; 26: 1183-88.
133. Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonist drugs. Stroke 1995; 26: 503-13.
134. Leach MJ, Swan JH, Eisenthal D, Dopson M, Nobbs M. BW619C89, a glutamate release inhibitor, protects against focal cerebral ischaemic damage. Stroke 1993; 24: 1063-67.
135. Muir KW, Hamilton SJC, Lunnon MW, Hobbiger S, Lees KR. Safety and tolerability of 619C89 after acute stroke. Cerebrovasc Dis 1998; 8: 31-37.
136. Nellgard B, Wieloch T. Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in the rat brain following transient severe cerebral ischemia. J Cereb Blood Flow Metab 1992; 12: 2-11.
137. Buchan AM, Lesiuk H, Barnes KA et al. AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists? Stroke 1993; 24: 1148-52.
138. Xue D, Huang ZG, Barnes K, Lesiuk HJ, Smith KE, Buchan AM. Delayed treatment with AMPA, but not NMDA, antagonists reduces neocortical infarction. J Cereb Blood Flow Metab 1994; 14: 251-61.
139. Gill R. The pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate antagonists and their role in cerebral ischaemia. Cerebrovasc Brain Metab Rev 1994; 6: 225-56.
140. Browne SE, McCulloch J. AMPA receptor antagonists and local cerebral glucose utilization in the rat. Brain Res 1994; 641: 10-20.
141. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of super-oxide and nitric oxide. J Biol Chem 1991; 266: 4244-50.
142. Zhang J, Dawson VL, Dawson TM, Snyder SH. Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 1994; 263: 687-89.
143. Eliasson MJL, Sampei K, Mandir AS. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischaemia. Nat Med 1997; 3: 1089-95.
144. Charles IG, Scorer CA, Moro MA et al. Expression of human nitric oxide synthase isozymes. Methods Enzymol 1996; 268: 449-60.
145. Forstermann U, Gath I. Purification of isoforms of nitric oxide synthase. Methods Enzymol 1996; 268: 334-39.
146. Fan B, Wang J, Stuehr DJ, Rousseau DL. NO synthase isozymes have distinct substrate binding sites. Biochemistry 1997; 36(42): 12660-65.
147. Huang ZH, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 1994; 265: 1883-85.
148. Samdani AF, Dawson MD, Dawson VL. Nitric oxide synthase in models of focal ischemia. Stroke 1997; 28: 1283-88.
149. Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci 1997; 20: 132-39.
150. Dawson DA. Nitric oxide and focal cerebral ischemia: Multiplicity of actions and diverse outcome. Cerebrovasc Brain Metab Rev 1994; 6: 299-324.
151. Morikawa E, Huang Z, Moskowitz MA. L-Arginine decreases infarct size caused by middle cerebral artery occlusion in SHR. Am J Physiol 1992; 263: H1632-35.
152. Morikawa E, Moskowitz MA, Huang Z et al. L-Arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat. Stroke 1994; 25: 429-35.
153. Zhang F, White JG, Iadecola C. Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia. J Cereb Blood Flow Metab 1994; 14: 217-26.
154. Zhang F, Iadecola C. Reduction of focal cerebral ischemic damage by delayed treatment with nitric oxide doors. J Cereb Blood Flow Metab 1994; 14: 574-80.
155. Iadecola C, Zhang F, Xu X. Inhibition of inducible nitric oxide synthase ameliorates cerebral nitric oxide damage. Am J Physiol 1995; 268: R286-92.
156. Iadecola C, Zhang FY, Casey R, Clark HB, Ross ME. Inducible nitric-oxide synthase gene-expression in vascular cells after transient focal cerebral-ischemia. Stroke 1996; 27: 1373-80.
157. Southan GJ, Szabo C. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem Pharmacol 1996; 51: 383-94.
158. Zhang FY, Casey RM, Ross ME, Iadecola C. Aminoguanidine ameliorates and L-arginine worsens brain-damage from intraluminal middle cerebral-artery occlusion. Stroke 1996; 27: 317-23.
159. De Ryck M. Protection of neurological function in stroke models and neuroprotective properties of lubeluzole. In: Hacke W (ed). Neuroprotective strategies for early intervention in acute ischaemic stroke. Cerebrovasc Dis 1997; 7: (suppl 2): 18-30.
160. Lesage AS, Peelers L, Leysen JE, Lubeluzole, a novel long-term neuroprotectant, inhibits the glutamate-activated nitric oxide synthase pathway. J Pharmacol Exp Ther 1996; 279: 759-66.
161. Buchkremer-Ratzmann I, Witte OW. Pharmacological reduction of electrophysiological diaschisis after photothrombotic ischemia in rat neocortex. Eur J Pharmacol 1997; 320: 103-109.
162. Scheller DKA, De Ryck M, Kolb J et al. Lubeluzole blocks increases in extracellular glutamate and taurine in the peri-infarct zone in rats. Eur J Pharmacol 1997; 338: 243-51.
163. Grotta J, for the US and Canadian Lubeluzole Ischemic Stroke Study Group. Lubeluzole treatment of acute ischemic stroke. Stroke 1997; 28: 2338-46.
164. Wahlgren N, for the CLASS Group. The Chlomethiazole Acute Stroke Study (CLASS): results of a randomised controlled study of chlomethiazole vs placebo in 1,360 patients. Cerebrovasc Dis 1997; 7 (suppl 4): 19.
165. De Deyn P, De Reuck J, Deberdt W, Vlietinck R, Orgogozo J-M, for the Piracetam in Acute Stroke Study (PASS) Group. Treatment of acute ischemic stroke with piracetam. Stroke 1997; 28: 2347-52.
166. Admani AK. New approach to treatment of recent stroke. BMJ 1978; ii: 1678-79.
167. Steiner TJ, Clifford Rose F. Towards a model stroke trial. The single centre naftidrofuryl study. Neuroepidemiol 1986; 5: 121-47.
168. Gray CS, French JM, Venables GS, Cartlidge NE, James OF, Bates D. A randomized double-blind controlled trial of naftidrofuryl in acute stroke. Age Ageing 1990; 19(6): 356-63.
169. Frampton JE, Brogden RN. Pentoxifylline (oxpentifylline). A review of its therapeutic efficacy in the management of peripheral vascular and cerebrovascular disorders. Drugs Aging 1995; 7: 480-503.
170. Black RS, Barclay LL, Nolan KA, Thaler HT, Hardiman ST, Blass JP. Pentoxifylline in cerebrovascular dementia. J Am Geriatr Soc 1992; 40(3): 237-44.
171. Hsu CY, Norris JW, Hogan EL et al. Pentoxifylline in acute non-hemorrhagic stroke. A randomized, placebo-controlled double-blind trial [see comments]. Stroke 1988; 19: 716-22.
172. Bogousslavsky J, Brott T, Diener HC et al. European strategies for early intervention in stroke - a report of an ad-hoc consensus group meeting. Cerebrovasc Dis 1996; 6: 315-24.
173. Adams HP Jr. The importance of the Helsingborg declaration on stroke management in Europe. J Intern Med 1996; 240: 169-71.
174. Haley EC Jr, Putman S, Anderson F et al. Safety study of tirilazad mesylate in patients with acute ischemic stroke (STIPAS). Stroke 1994; 25: 418-23.
175. The RANTTAS Investigators. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS): Stroke 1996; 27: 1453-58.
176. Yamaguchi T, Sano K, Takakura K et al. Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke 1998; 29: 12-17.
177. Dugan LL, Turetsky DM, Du C et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci USA 1997; 94: 9434-39.
178. Dugan LL, Creedon DJ, Johnson EM Jr, Holtzman DM. Rapid suppression of free radical formation by nerve growth factor involves the mitogen-activated protein kinase pathway. Proc Natl Acad Sci USA 1997; 94: 4086-91.
179. Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian LA, for the Citicoline Stroke Study Group. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Neurology 1997; 49: 671-78.
180. Tarkowski E, Rosengren L, Blomstrand C et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 1995; 26: 1343-98.
181. Lindsberg PJ, Carpen O, Paetau A, Karjalainen-Lindsberg ML, Kaste M. Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation 1996; 94: 939-45.
182. Kim JS. Cytokines and adhesion molecules in stroke and related diseases. J Neurol Sci 1996; 137: 69-78.
183. Tarkowski E, Rosengren L, Blomstrand C et al. Intrathecal release of pro- and anti-inflammatory cytokines during stroke. Clin Exp Immunol 1997; 110: 492-99.
184. Barone FC, Arvin B, White RF et al. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 1997; 28: 1233-44.
185. Yamasaki Y, Matsuo Y, Zagorski J et al. New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats. Brain Res 1997; 759: 103-11.
186. Meistrell ME 3rd, Botchkina GI, Wang H et al. Tumor necrosis factors is brain damaging cytokine in cerebral ischemia. Shock 1997; 8: 341-48.
187. Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab 1998; 18: 52-58.
188. Chopp M, Li Y, Jiang N, Zhang RI, Prostak J. Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metab 1996; 16: 578-84.
189. Enlimomab Acute Stroke Trial Investigators. The Enlimomab Acute Stroke Trial: final results. Cerebrovasc Dis 1997; 7 (suppl 4): 18.
190. Wang X, Barone FC, Aiyar NV, Feuerstein GZ. Interleukin-1 receptor and receptor antagonist gene expression after focal stroke in rats. Stroke 1997; 28: 155-61 [discussion 161-62].
191. Schubert P, Ogata T, Marchini C, Ferroni S, Rudolphi K. Protective mechanisms of adenosine in neurons and glial cells. Ann N Y Acad Sci 1997; 825: 1-10.
192. Skaper SD, Leon A. Monosialogangliosides, neuroprotcction, and neuronal repair processes [Review]. J Neurotrauma 1992; 9 (suppl 2): S507-16.
193. Candelise L, Ciccone A. Gangliosides in acute ischaemic stroke. In: Warlow C, van Gijn J, Sandercock P, Candelise L, Langhome P (eds). Stroke module of the Cochrane database of systematic reviews. The Coehrane Collaboration; Issue 3. Oxford: Update Software, 1997.
194. Feeney DM, Sutton RL. Pharmacotherapy for recovery of function after brain injury. Crit Rev Neurobiol 1987; 3: 135-97.
195. Dorman PJ, Sandercock PA. Considerations in the design of clinical trials of neuroprotective therapy in acute stroke. Stroke 1996; 27: 1507-15.