Pharmacological Neuroprotection in Acute Ischemic Stroke

1. Ginsberg MD. Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 2008; 55(3): 363–389.

2. Arundine M, Tymianski M. Molecular mechanism of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci 2004; 61(6): 657–668.

3. Dawson DA, Wadsworth G, Palmer AM. A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke. Brain Res 2001; 892(2): 344–350.

4. Labiche LA, Grotta JC. Clinical trials for cytoprotection in stroke. NeoroRx 2004; 1(1): 46–70.

5. Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB et al. Safety and tolerability of the glutamate antagonist CGS 19755 (Seltofel) in patients with acute ischemic stroke. Result of a phase II a randomized trial. Stroke 1995; 26(4): 602–605.

6. Pérez-Pinzón MA, Maier CM, Yoon EJ, Sun GH, Giffard RG, Steinberg GK. Correlation of CGS 19755 neuroprotection against in vitro excitotoxicity and focal cerebral ischemia. J Cereb Blood Flow Metab 1995; 15(5): 865–876.

7. Albers GW, Atkinson RP, Kelley RF, Rosenbaum DM. Safety, tolerability and pharmacokinetics of the N-methyl-D-aspartate antagonist dextrorphan in patients with acute stroke. Dextrorphan Study Group. Stroke 1995; 26(2): 254–258.

8. Muir KW, Grosset DG, Lees KR. Clinical pharmacology of CNS 1102 in volunteers. Ann N Y Acad Sci 1995; 765: 279–289.

9. Albers GW, Goldstein LB, Hall D, Lesko LM. Aptinagel hydrochloride in acute ischemic stroke: a randomized controlled trial. JAMA 2001; 286(21): 2673–2682.

10. Ovbiagele B, Kidwell CS, Starkman S, Saver JL. Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep 2003; 3(1): 9–20.

11. Kidwell CS, Lees KR, Muir KW, Chen C, Davis SM, De Silva DA et al. Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial. Stroke 2009; 40(5): 1704–1709.

12. Saver JL, Kidwell C, Eckstein M, Starkman S; FAST-MAG Pilot Trial Investigators. Prehospital neuroprotective therapy for acute stroke: results of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) pilot trial. Stroke 2004; 35(5): e106–e108.

13. Stewart D, Marder VJ, Starkman S, Saver JL. Magnesium sulfate neither potentiates nor inhibits tissue plasminogen activator-induced thrombolysis. J Tromb Haemost 2006; 4(7): 1575–1579.

14. Sacco RL, DeRosa JT, Haley EC, jr, Levin B, Ordronneau P, Phillips SJ et al. Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial. JAMA 2001; 285(13): 1719–1728.

15. Lees KR, Asplund K, Carolei A, Davis SM, Diener HC, Kaste M et al. Glycine antagonist (gavestinel) in neuroprotection (GAIN international) in patients with acute stroke: a randomized controlled trial. GAIN International Investigators. Lancet 2000; 355(9219): 1949–1954.

16. Warach S, Kaufman D, Chiu D, Devlin T, Luby M, Rashid A et al. Effect of the glycine antagonist Gavestinel on cerebral infarcts in acute stroke patients, a randomized placebo-controlled trial: The GAIN MRI Substudy. Cerebrovasc Dis 2006; 4821(1–2): 106–111.

17. Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology 1997; 49 (Suppl 4): S66–S69.

18. Muir KW, Holzapfel L, Lees KR, Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke. Cerebrovasc Dis 2000; 10(6): 431–436.

19. Lesage AS, Peeters L, Leysen JE. Lubeluzole, a novel long-term neuroprotectant, inhibits the glutamate-activated nitric oxide synthase pathway. J Pharmacol Exp Ther 1996; 279(2): 759–766.

20. Grotta J. Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzol Ischemic Stroke Study Group. Stroke 1997; 28(12): 2338–2346.

21. Diener HC. Multinational randomized controlled trial of lubeluzole in acute ischaemic stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group. Cerebrovasc Dis 1998; 8(3): 172–181.

22. Diener HC, Cortens M, Ford G, Grotta J, Hacke W, Kaste M et al. Lubeluzole in acute ischemic stroke treatment: A double-blind study with an 8-hour inclusion window comparing a 10- mg daily dose of lubeluzol with placebo. Stroke 2000; 31(11): 2543–2551.

23. Gandolfo C, Sandercock P, Conti M. Lubeluzole for acute ischemic stroke. Cochrane Database Syst Rev 2002; 1: CD001924.

24. Turski L, Huth A, Sheardown M, McDonald F, Neuhaus R, Schneider HH et al. ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proc Natl Acad Sci USA 1998; 95(18):10960–10965.

25. Sydserff SG, Cross AJ, Green AR. The neuroprotective effect of chlormethiazole on ischaemic neuronal damage following permanent middle cerebral artery ischaemia in the rat. Neurodegeneration 1995; 4(3): 323–328.

26. Wahlgren NG, Ranasinha KW, Rosolacci T, Franke CL, van Erven PM, Ashwood T et al. Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 1999; 30(1): 21–28.

27. Lyden P, Shuaib A, Ng K, Levin K, Atkinson RP, Rajput A et al. CLASS-I/H/T Investigators. Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results. Stroke 2002; 33(1): 122–128.

28. Lyden P, Jacoby M, Schim J, Albers G, Mazzeo P, Ashwood T et al. The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results. Neurology 2001; 57(7): 1199–1205.

29. Lodder J, van Raak L, Hilton A, Hardy E, Kessels A. Diazepam to improve acute stroke outcome: results of the early GABA-ergic activation study in stroke trial. A randomized double-blind placebo-controlled trial. Cerebrovasc Dis 2006; 21(1–2): 120–127.

30. Costa C, Leone G, Saulle E, Pisani F, Bernardi G, Calabresi P. Coactivation of GABA(A) and GABA(B) receptor results in neuroprotection during in vitro ischemia. Stroke 2004; 35(2): 596–600.

31. Squire IB, Lees KR, Pryse-Phillips W, Kertesz A, Bamford J. The effects of lifarizine in acute cerebral infarction: a pilot safety study. Cerebrovasc Dis 1996; 6: 156–160.

32. Davies MF, Deisz RA, Prince DA, Peroutka SJ. Two distinct effects of 5-hydroxytryptamine on single cortical neurons. Brain Res 1987; 423(1–2): 347–352.

33. Ginsberg MD. Neuroprotection in brain ischemia – an update – Parts I and II. Neuroscientist 1995; 95(1): 103–164.

34. Ramirez-Lessepas M, Patrick BK, Snyder BD, Lakatua DJ. Failure of central nervous system serotonin blockage to influence outcome in acute cerebral infarction. A double blind randomized trial. Stroke 1986; 17(5): 953–956.

35. Fallis RJ, Fisher M, Lobo RA. A double blind trial of naloxone in the treatment of acute stroke. Stroke 1984; 15(4): 627–629.

36. Olinger CP, Adams HP jr, Brott TG, Biller J, Barsan WG, Toffol GJ et al. High-dose intravenous naloxone for the treatment of acute ischemic stroke. Stroke 1990; 21(5): 721–725.

37. Clark W, Ertag W, Orecchio E, Raps E. Cervene in acute ischemic stroke: results of a double-blind, placebo-controlled, dose-comparison study. J Stroke Cerebrovasc Dis 1999; 8(4): 224–230.

38. Clark WM, Raps EC, Tong DC, Kelly RE. Cervene (Nalmefene) in acute ischemic stroke: final results of a phase III efficacy study. The Cervene Stroke Study Investigators. Stroke 2000; 31(6): 1234–1239.

39. Trust Study Group. Randomised double-blind, placebo-controlled trial on Nimodipine in acute stroke. Lancet 1990; 336(8725): 1205–1209.

40. American Nimodipine Study Group. Clinical trial of nimodipine in acute ischemic stroke. Stroke 1992; 23(1): 3–8.

41. Kaste M, Fogelholm R, Erilä T, Palomäki H, Murros K, Rissanen A et al. A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke. Stroke 1994; 25(7): 1348–1353.

42. Wahlgren NG, Ranasinha KW, Rosolacci T, Franke CL, van Erven PM, Ashwood T et al. Intravenous Nimodipine West European Stroke Trial (INWEST) on nimodipine in the treatment of acute ischaemic stroke. Cerebrovasc Dis 1994; 15(4): 204–210.

43. Mohr JP, Orgogozo JM, Harrison MJG, Hennerici M, Wahlgren NG, Gelmers HJ et al. Meta-analysis of oral nimodipine trials in acute ischemic stroke. Cerebrovasc Dis 1994; 4: 197–203.

44. Horn J, de Haan RJ, Vermeulen M, Limburg M. Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial. Stroke 2001; 32(2): 461–465.

45. Horn J, Limburg M. Calcium antagonists for acute ischemic stroke. Cochrane Database Syst Rev 2000; 2: CD001928.

46. Feigin VL, Rinkel GJ, Algra A, Vermeulen M, van Gijn J. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2000; 2: CD000277.

47. Franke CL, Palm R, Dalby M, Schoonderwaldt HC, Hantson L, Eriksson B et al. Flunarizin in stroke treatment (FIST): a double-blind placebo-controlled trial in Scandinavia and the Netherlands. Acta Neurol Scand 1996; 93(1): 56–60.

48. Bozik M, Hommel M, Grotta J et al. Efficacy and safety of MaxiPost in patients with acute stroke. J Neurol Sci 2001; 187: S252.

49. Lees KR, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener HC et al. NXY-059 for acute ischemic stroke. N Engl J Med 2006; 354(6): 588–600.

50. Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM et al. NXY-059 for the treatment of acute ischemic stroke. N Engl J Med 2007; 357(6): 562–571.

51. The RANTTAS Investigators. A randomized trial of tirilazad mesilate in patients with acute stroke (RANTTAS). The RANTTAS Investigators. Stroke 1996; 27(9): 1453–1458.

52. van der Worp HB, Kappelle LJ, Algra A, Bär PR, Orgogozo JM, Ringelstein EB et al. The effect of tirilazad mesylate on infarct volume of patients with acute ischemic stroke. Neurology 2002; 58(1): 133–135.

53. Tirilazad International Steering Committee. Tirilazad mesylate in acute ischemic stroke: A systematic review. Stroke 2000; 31(9): 2257–2265.

54. Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T et al. Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke 1998; 29(1): 12–17.

55. Edaravone Acute Infarction Study. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo controlled, double blind study at multicenters. Cerebrovasc Dis 2003; 15(3): 222–229.

56. Wang KK, Larner SF, Robinson G, Hayes RL. Neuroprotection targets after traumatic brain injury. Curr Opin Neurol 2006; 19(6): 514–519.

57. Ehler E. Cévní mozkové příhody – neuroprotektivní léčba. Neurol pro praxi 2001; 4: 173–177.

58. Furuya K, Takeda H, Azhar S, McCarron RM, Chen Y, Ruetzler CA 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 2001; 32(11): 2665–2674.

59. Zhang RL, Chopp M, Jiang N, Tang WX, Prostak J, Manning AM 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 1995; 26(8): 1438–1442.

60. Krams M, Lees KR, Hacke W, Grieve AP, Orgogozo JM, Ford GA. Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute ischemic stroke. Stroke 2003; 34(11): 2543–2548.

61. Sughrue ME, Connolly ES jr. Effectively bridging the preclinical/clinical gap: the results of the ASTIN trial. Stroke 2004; 35(4): e81–e82.

62. Jiang N, Chopp M, Chahwala S. Neutrophil inhibitory factor treatment of focal cerebral ischemia in the rat. Brain Res 1998; 788(1–2): 25–34.

63. Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999; 96(23): 13496–13500.

64. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology 2007; 69(14): 1404–1410.

65. 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 1999; 274(48): 34450–34458.

66. Norris JW, Hachinski VC. High dose steroid treatment in cerebral infarction. Br Med J 1986; 292(6512): 21–23.

67. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C et al. Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol 1997; 11(9): 1245–1255.

68. Qizilbash N, Lewington SL, Lopez-Arrieta JM. Corticosteroids for acute ischaemic stroke. Cochrane Databae Sys Rev 2000; 2: CD000064.

69. Hsu CY, Norris JW, Hogan EL, Bladin P, Dinsdale HB, Yatsu FM et al. Pentoxifylline in acute nonhemorrhagic stroke. A randomized, placebo-controlled double-blind trial. Stroke 1988; 19(6): 716–722.

70. European Pentoxifylline Multi-Infarct Dementia Study group. European Pentoxifylline Multi-Infarct Dementia Study. Eur Neurol 1996; 36(5): 315–321.

71. SASS Trial group. Ganglioside GM1 in acute ischemic stroke. The SASS trial. Stroke 1994; 25(6): 1141–1148.

72. Argentino C, Sacchetti ML, Toni D, Savoini G, D’Arcangelo E, Erminio F et al. GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study – Hemodilution + Drug. Stroke 1989; 20(9): 1143–1149.

73. Lenzi GL, Grigoletto F, Gent M, Roberts RS, Walker MD, Easton JD et al. Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial. Stroke 1994; 25(8): 1552–1558.

74. Candelise L, Ciccone A. Gangliosides for acute ischaemic stroke. Cochrane Database Syst Rev 2001; 4: CD000094.

75. Wronski R, Tompa P, Hutter-Paier B, Crailsheim K, Friedrich P, Windisch M. Inhibitory effect of a brain derived peptide preparation on the Ca++-dependent protease, calpain. J Neural Transm 2000; 107(2): 145–157.

76. Skvortsova VI, Stakhovskaia LV, Gubskii LV, Shamalov NA, Tikhonova IV, Smychkov AS. A randomized, double-blind, placebo-controlled study of Cerebrolysin safety and efficacy in the treatment of acute ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova 2004; (Suppl 11): 51–55.

77. Ladurner G, Kalvach P, Moessler H. Neuroprotective treatment with cerebrolysin in patients with acute stroke: a randomised controlled trial. J Neural Transm 2005; 112(3): 415–428.

78. Hong Z, Moessler H, Bornstein N, Brainin M, Heiss WD. A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia – CASTA. Int J Stroke 2009; 4(5): 406–412.

79. De Deyn PP, Reuck JD, Deberdt W, Vlietinck R, Orgogozo JM. Treatment of acute ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study (PASS) Group. Stroke 1997; 28(12): 2347–2352.

80. Ricci S, Celani MG, Cantisani AT, Righetti E. Piracetam for acute ischaemic stroke. Cochrane Database Syst Rev 2006; 2: CD000419.

81. Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 2000; 97(19): 10526–10531.

82. Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian LA. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group. Neurology 1997; 49(3): 671–678.

83. Clark WM, Williams BJ, Selzer KA, Zweifler RM, Sabounjian LA, Gammans RE. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 1999; 30(12): 2592–2597.

84. Clark WM, Wechsler LR, Sabounjian LA, Schwiderski UE; Citicoline Stroke Study Group. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001; 57(9): 1595–1602.

85. Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, Sabounjian L et al. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol 2000; 48(5): 713–722.

86. Corso EA, Arena M, Ventimiglia A, Bizzarro G, Campo G, Rodolico F. CDP choline in cerebral vasculopathy: clinical evaluation and instrumental semeiology. Clin Ter 1982; 102(4): 379–386.

87. Kawamata T, Ren J, Chan TC, Charette M, Finklestein SP. Intracisternal osteogenic protein-1 enhances functional recovery following focal stroke. Neuroreport 1998; 9(7): 1441–1445.

88. Song BW, Vinters HV, Wu D, Pardridge WM. 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 2002; 301(2): 605–610.

89. Fisher M, Schaebitz W. An overview of acute stroke therapy. Arch Intern Med 2000; 160(21): 3196–3205.

90. Bogousslavsky J, Victor SJ, Salinas EO, Pallay A, Donnan GA, Fieschi C et al. Fiblast (trafermin) in acute stroke: results of the European-Australian phase II/III safety and efficacy trial. Cerebrovasc Dis 2002; 14(3–4): 239–251.

91. Martin-Schild S, Hallevi H, Shaltoni H, Barreto AD, Gonzales NR, Aronowski J et al. Combined neuroprotective modalities coupled with thrombolysis in acute ischemic stroke: a pilot study of caffeinol and mild hypothermia. J Stroke Cerebrovasc Dis 2009; 18(2): 86–96.

92. Aronowski J, Strong R, Shirzadi A, Grotta JC. Ethanol plus caffeine (caffeinol) for treatment of ischemic stroke: preclinical experience. Stroke 2003; 34(5): 1246–1251.

93. Palesch YY, Hill MD, Ryckborst KJ, Tamariz D, Ginsberg MD. The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis. Stroke 2006; 37(8): 2107–2114.

94. Ginsberg MD, Hill MD, Palesch YY, Ryckborst KJ, Tamariz D. The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke – I: Physiological responses and safety results. Stroke 2006; 37(8): 2100–2106.

95. Kalvach a kol. Mozkové ischémie a hemoragie. 3rd ed. Praha: Grada Publishing 2010.

96. van der Most PJ, Dolga AM, Nijholt IM, Luiten PG, Eisel UL. Statins: mechanisms of neuroprotection. Prog Neurobiol 2009; 88(1): 64–75.

97. Elkind MS, Sacco RL, Macarthur RB, Peerschke E, Neils G, Andrews H et al. High-dose lovastatin for acute ischemic stroke: results of the phase I dose escalation neuroprotection with statin therapy for acute recovery trial (NeuSTART). Cerebrovasc Dis 2009; 28(3): 266–275.

98. Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 2009; 8(5): 491–500.

99. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8(9): 963–970.

100. Padma Srivastava MV. Restorative therapy in stroke using stem cells. Neurol India 2009; 57(4): 381–386.

101. Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J et al. Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000; 55(4): 565–569.

102. Locatelli F, Bersano A, Ballabio E, Lanfranconi S, Papadimitriou D, Strazzer S et al. Stem cell therapy in stroke. Cell Mol Life Sci 2009; 66(5): 757–772.

103. Kalita Z a kol. Akutní cévní mozkové příhody. Praha: Maxdorf Jessenius 2006.

104. Suzuki J, Imaizumi S, Kayama T, Yoshimoto T.Chemiluminescence in hypoxic brain--the second report: cerebral protective effect of mannitol, vitamin E and glucocorticoid. Stroke 1985; 16(4): 695–700.