Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia

Annals of Neurology

Volumn 54, Issue 3, 2003, Pages 330-342

  Ginsberg, Myron D ^a   Becker, David A ^b   Busto, Raul ^a   Belayev, Andrey ^a   Zhang, Yongbo ^a   Khoutorova, Larissa ^a   Ley, James J ^b   Zhao, Weizhao ^a   Belayev, Ludmila ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b FLORIDA INTERNATIONAL UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; AZULENYL NITRONE; DIMETHYL SULFOXIDE; DISUFENTON SODIUM; NITRONE DERIVATIVE; SODIUM CHLORIDE; STILBAZULENYL NITRONE; UNCLASSIFIED DRUG;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN INFARCTION; BRAIN ISCHEMIA; CONTROLLED STUDY; DRUG EFFICACY; LIPOPHILICITY; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT; REGRESSION ANALYSIS; SCORING SYSTEM; STROKE;

ANIMALS; ANTIOXIDANTS; BEHAVIOR, ANIMAL; BRAIN; BRAIN EDEMA; DIMETHYL SULFOXIDE; DISEASE MODELS, ANIMAL; FREE RADICAL SCAVENGERS; IMAGE PROCESSING, COMPUTER-ASSISTED; INFARCTION, MIDDLE CEREBRAL ARTERY; MALE; NEUROPROTECTIVE AGENTS; NITROGEN OXIDES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 0042837942     PISSN: 03645134     EISSN: None     Source Type: Journal    
DOI: 10.1002/ana.10659     Document Type: Article

References (84)

1. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985;312:159-163.
2. Siesjo BK, Agardh CD, Bengtsson F. Free radicals and brain damage. Cerebrovasc Brain Metab Rev 1989;1:165-211.
3. Small DL, Morley P, Buchan AM. Biology of ischemic cerebral cell death. Prog Cardiovasc Dis 1999;42:185-207.
4. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 2001;21: 2-14.
5. Lefer DJ, Granger DN. Oxidative stress and cardiac disease. Am J Med 2000;109:315-323.
6. Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg 2001;181:160-166.
7. Schoenberg MH, Beger HG. Reperfusion injury after intestinal ischemia. Crit Care Med 1993;21:1376-1386.
8. Nath KA, Norby SM. Reactive oxygen species and acute renal failure. Am J Med 2000;109:665-678.
9. Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson's disease. Neurology 1996;47:S161-S170.
10. Pratico D, Delanty N. Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. Am J Med 2000;109:577-585.
11. Beal MF. Oxidatively modified proteins in aging and disease. Free Radic Biol Med 2002;32:797-803.
12. Young B, Runge JW, Waxman KS, et al. Effects of pegorgotein on neurologic outcome of patients with severe head injury. A multicenter, randomized controlled trial. JAMA 1996;276: 538-543.
13. Ogawa A, Yoshimoto T, Kikuchi H, et al. Ebselen in acute middle cerebral artery occlusion: a placebo-controlled, double-blind clinical trial. Cerebrovasc Dis 1999;9:112-118.
14. Tirilazad International Steering Committee. Tirilazad mesylate in acute ischemic stroke: a systematic review. Stroke 2000;31: 2257-2265.
15. Hensley K, Carney JM, Stewart CA, et al. Nitrone-based free radical traps as neuroprotective agents in cerebral ischaemia and other pathologies. Int Rev Neurobiol 1997;40:299-317.
16. Novelli GP, Angiolini P, Tani R, et al. Phenyl-T-butyl-nitrone is active against traumatic shock in rats. Free Radic Res Commun 1986;1:321-327.
17. Kuroda S, Tsuchidate R, Smith ML, et al. Neuroprotective effects of a novel nitrone, NXY-059, after transient focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1999;19: 778-787.
18. Becker DA. Highly sensitive colorimetric detection and facile isolation of diamagnetic free radical adducts of novel chromotropic nitrone spin trapping agents readily derived from guaiazulene. J Am Chem Soc 1996;118:905-906.
19. Becker DA. Aspects of the chemistry and biology of azulenyl nitrones, a newly synthesized class of spin-trapping agents. In: Organic synthesis: theory and applications. Vol 4. Greenwich, CT: JAI, 1998:155-177, Hudlicky T (ed.)
20. Althaus JS, Fleck TJ, Becker DA, et al. Azulenyl nitrones: colorimetric detection of oxyradical end products and neuroprotection in the gerbil transient forebrain ischemia/reperfusion model. Free Radic Biol Med 1998;24:738-744.
21. Klivenyi P, Matthews RT, Wermer M, et al. Azulenyl nitrone spin traps protect against MPTP neurotoxicity. Exp Neurol 1998;152:163-166.
22. Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 1993;300:535-543.
23. Becker DA, Natero R, Echegoyen L, Lawson RC. Redox behaviour of azulenyl nitrones: fully reversible one electron oxidation by cyclic voltammetry at potentials in the range of biological antioxidants. J Chem Soc, Perkin Trans I 1998;2: 1289-1291.
24. Simic MG. Antioxidant compounds: an overview. In: Oxidative damage and repair: chemical, biological, and medicinal aspects. New York: Pergamon Press, 1991:47-56, Davies KJA (ed.)
25. Becker DA. Diagnostic and therapeutic applications of azulenyl nitrone spin traps. Cell Mol Life Sci 1999;56:626-633.
26. Castagne V, Lefevre K, Natero R, et al. An optimal redox status for the survival of axotomized ganglion cells in the developing retina. Neuroscience 1999;93:313-320.
27. Becker DA, Ley JJ, Echegoyen L, Alvarado R. Stilbazulenyl nitrone (STAZN): a nitronyl-substituted hydrocarbon with the potency of classical phenolic chain-breaking antioxidants. J Am Chem Soc 2002;124:4678-4684.
28. Belayev L, Becker DA, Alonso OF, et al. Stilbazulenyl nitrone, a novel azulenyl nitrone antioxidant: improved neurological deficit and reduced contusion size after traumatic brain injury in rats. J Neurosurg 2002;96:1077-1083.
29. Busto R, Dietrich WD, Globus MY, et al. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 1987; 7:729-738.
30. Belayev L, Alonso OF, Busto R, et al. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 1996;27: 1616-1622.
31. Belayev L, Liu Y, Zhao W, et al. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke 2001; 32:553-560.
32. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989;20:84-91.
33. Belayev L, Busto R, Ikeda M, et al. Protection against blood-brain barrier disruption in focal cerebral ischemia by the type IV phosphodiesterase inhibitor BBB022: a quantitative study. Brain Res 1998;787:277-285.
34. Belayev L, Zhao W, Pattany PM, et al. Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia. Stroke 1998;29:2587-2599.
35. Huh PW, Belayev L, Zhao W, et al. Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. J Neurosurg 2000; 92:91-99.
36. Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986;17:472-476.
37. De Ryck M, Van Reempts J, Borgers M, et al. Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats. Stroke 1989;20:1383-1390.
38. Swanson RA, Morton MT, Tsao-Wu G, et al. A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 1990;10:290-293.
39. Lin TN, He YY, Wu G, et al. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 1993; 24:117-121.
40. Belayev L, Khoutorova L, Deisher TA, et al. The neuroprotective effect of solCD39, a novel platelet aggregation inhibitor, on transient middle cerebral artery occlusion in rats. Stroke 2003; 34:758-763.
41. Zhao W, Ginsberg MD, Prado R, Belayev L. Depiction of infarct frequency distribution by computer-assisted image mapping in rat brains with middle cerebral artery occlusion. Comparison of photothrombotic and intraluminal suture models. Stroke 1996;27:1112-1117.
42. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. New Engl J Med 1995;333: 1581-1587.
43. Barone FC, Feuerstein GZ, White RF. Brain cooling during transient focal ischemia provides complete neuroprotection. Neurosci Biobehav Rev 1997;21:31-44.
44. Yrjanheikki J, Tikka T, Keinanen R, et al. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-13500.
45. Steinberg GK, Yoon EJ, Kunis DM, et al. Neuroprotection by N-methyl-D-aspartate antagonists in focal cerebral ischemia is dependent on continued maintenance dosing. Neuroscience 1995;64:99-107.
46. Small DL, Buchan AM. NMDA antagonists: their role in neuroprotection. Int Rev Neurobiol 1997;40:137-171.
47. Kobayashi T, Mori Y. Ca2+ channel antagonists and neuroprotection from cerebral ischemia. Eur J Pharmacol 1998;363: 1-15.
48. Beck T, Bielenberg GW. The effects of two 21-aminosteroids on overt infarct size 48 hours after middle cerebral artery occlusion in the rat. Brain Res 1991;560:159-162.
49. Lesiuk H, Sutherland G, Peeling J, et al. Effect of U74006F on forebrain ischemia in rats. Stroke 1991;22:896-901.
50. Novelli GP, Angiolini P, Livi P, Paternostro E. Oxygen-derived free radicals in the pathogenesis of experimental shock. Resuscitation 1989;18:195-205.
51. Hearse DJ, Tosaki A. Free radicals and reperfusion-induced arrhythmias: protection by spin trap agent PBN in the rat heart. Circ Res 1987;60:375-383.
52. Clough-Helfman C, Phillis JW. The free radical trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) attenuates cerebral ischaemic injury in gerbils. Free Radic Res Commun 1991;15: 177-186.
53. Phillis JW, Clough-Helfman C. Protection from cerebral ischemic injury in gerbils with the spin trap agent N-tert-butyl-alpha-phenylnitrone (PBN). Neurosci Lett 1990;116: 315-319.
54. Carney JM, Starke-Reed PE, Oliver CN, et al. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA 1991;88: 3633-3636.
55. Carney JM, Floyd RA. Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone (PBN) and other spintrapping agents: a novel series of nonlipid free radical scavengers. J Mol Neurosci 1991;3:47-57.
56. Yue TL, Gu JL, Lysko PG, et al. Neuroprotective effects of phenyl-t-butyl-nitrone in gerbil global brain ischemia and in cultured rat cerebellar neurons. Brain Res 1992;574:193-197.
57. Cao X, Phillis JW. alpha-Phenyl-tert-butyl-nitrone reduces cortical infarct and edema in rats subjected to focal ischemia. Brain Res 1994;644:267-272.
58. Zhao Q, Pahlmark K, Smith ML, Siesjo BK. Delayed treatment with the spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) reduces infarct size following transient middle cerebral artery occlusion in rats. Acta Physiol Scand 1994;152:349-350.
59. Folbergrova J, Zhao Q, Katsura K, Siesjo BK. N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. Proc Natl Acad Sci USA 1995;92:5057-5061.
60. Kuroda S, Katsura K, Hillered L, et al. Delayed treatment with alpha-phenyl-N-tert-butyl nitrone (PBN) attenuates secondary mitochondrial dysfunction after transient focal cerebral ischemia in the rat. Neurobiol Dis 1996;3:149-157.
61. Yang Y, Li Q, Shuaib A. Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl) -nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol 2000;163:39-45.
62. Sen S, Goldman H, Morehead M, et al. alpha-Phenyl-tert-butyl-nitrone inhibits free radical release in brain concussion. Free Radic Biol Med 1994;16:685-691.
63. Marklund N, Clausen F, Lewen A, et al. alpha-Phenyl-tert-N-butyl nitrone (PBN) improves functional and morphological outcome after cortical contusion injury in the rat. Acta Neurochir (Wien) 2001;143:73-81.
64. Marklund N, Clausen F, McIntosh TK, Hillered L. Free radical scavenger posttreatment improves functional and morphological outcome after fluid percussion injury in the rat. J Neurotrauma 2001;18:821-832.
65. Pazos AJ, Green EJ, Busto R, et al. Effects of combined postischemic hypothermia and delayed N-tert-butyl-alpha-phenylnitrone (PBN) administration on histopathological and behavioral deficits associated with transient global ischemia in rats. Brain Res 1999;846:186-195.
66. Asahi M, Asahi K, Wang X, Lo EH. Reduction of tissue plasminogen activator-induced hemorrhage and brain injury by free radical spin trapping after embolic focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2000;20:452-457.
67. Lapchak PA, Chapman DF, Zivin JA. Pharmacological effects of the spin trap agents N-t-butyl-phenylnitrone (PBN) and 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) in a rabbit thromboembolic stroke model: combination studies with the thrombolytic tissue plasminogen activator. Stroke 2001;32: 147-153.
68. Maines MD, Raju VS, Panahian N. Spin trap (N-t-butyl-alpha-phenylnitrone)-mediated suprainduction of heme oxygenase-1 in kidney ischemia/reperfusion model: role of the oxygenase in protection against oxidative injury. J Pharmacol Exp Ther 1999;291:911-919.
69. Tsuji M, Inanami O, Kuwabara M. Neuroprotective effect of alpha-phenyl-N-tert-butylnitrone in gerbil hippocampus is mediated by the mitogen-activated protein kinase pathway and heat shock proteins. Neurosci Lett 2000;282:41-44.
70. Floyd RA, Hensley K. Nitrone inhibition of age-associated oxidative damage. Ann N Y Acad Sci 2000;899:222-237.
71. Floyd RA, Hensley K, Forster MJ, et al. Nitrones as neuroprotectants and antiaging drugs. Ann N Y Acad Sci 2002;959: 321-329.
72. Li PA, He QP, Nakamura L, Csiszar K. Free radical spin trap alpha-phenyl-N-tert-butyl-nitron inhibits caspase-3 activation and reduces brain damage following a severe forebrain ischemic injury. Free Radic Biol Med 2001;31:1191-1197.
73. Lees KR, Sharma AK, Barer D, et al. Tolerability and pharmacokinetics of the nitrone NXY-059 in patients with acute stroke. Stroke 2001;32:675-680.
74. Zhao Z, Cheng M, Maples KR, et al. NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat. Brain Res 2001;909: 46-50.
75. Marshall JW, Duffin KJ, Green AR, Ridley RM. NXY-059, a free radical-trapping agent, substantially lessens the functional disability resulting from cerebrall ischemia in a primate species. Stroke 2001;32:190-198.
76. Yoshimoto T, Kristian T, Hu B, et al. Effect of NXY-059 on secondary mitochondrial dysfunction after transient focal ischemia; comparison with cyclosporin A. Brain Res 2002;932: 99-109.
77. Sydserff SG, Borelli AR, Green AR, Cross AJ. Effect of NXY-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 2002; 135:103-112.
78. Shpall EJ, LeMaistre CF, Holland K, et al. A prospective randomized trial of buffy coat versus CD34-selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy. Blood 1997;90:4313-4320.
79. Vadhan-Raj S, Kavanagh JJ, Freedman RS, et al. Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study. Lancet 2002;359:2145-2152.
80. Repine JE, Pfenninger OW, Talmage DW, et al. Dimethyl sulfoxide prevents DNA nicking mediated by ionizing radiation or iron/hydrogen peroxide-generated hydroxyl radical. Proc Natl Acad Sci USA 1981;78:1001-1003.
81. Shimizu S, Simon RP, Graham SH. Dimethylsulfoxide (DMSO) treatment reduces infarction volume after permanent focal cerebral ischemia in rats. Neurosci Lett 1997;239: 125-127.
82. Little JR, Cook A, Lesser RP. Treatment of acute focal cerebral ischemia with dimethyl sulfoxide. Neurosurgery 1981;9:34-39.
83. Little JR, Spetzler RF, Roski RA, et al. Ineffectiveness of DMSO in treating experimental brain ischemia. Ann N Y Acad Sci 1983;411:269-277.
84. Lapchak PA, Araujo DM, Song D, Zivin JA. Neuroprotection by the selective cyclooxygenase-2 inhibitor SC-236 results in improvements in behavioral deficits induced by reversible spinal cord ischemia. Stroke 2001;32:1220-1225.