Neuroprotective effects of the novel brain-penetrating antioxidant U-101033E and the spin-trapping agent α-phenyl-N-tert-butyl nitrone (PBN)

Experimental Brain Research

Volumn 130, Issue 1, 2000, Pages 60-66

  Schmid Elsaesser, Robert ^a   Hungerhuber, Edwin ^a   Zausinger, Stefan ^a   Baethmann, Alexander ^a   Reulen, Hanns Juergen ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Antioxidants; Cerebral blood flow; Cerebral ischemia; Neuroprotection; Rats

Indexed keywords

2,4 DIAMINOPYRROLOPYRIMIDINE; ANTIOXIDANT; N TERT BUTYL ALPHA PHENYLNITRONE; PYRROLOPYRIMIDINE DERIVATIVE; SCAVENGER; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTERY OCCLUSION; ARTICLE; BLOOD BRAIN BARRIER; BRAIN ARTERY; BRAIN BLOOD FLOW; BRAIN FUNCTION; BRAIN INFARCTION; BRAIN ISCHEMIA; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; LASER DOPPLER FLOWMETRY; MALE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT;

EID: 0033951729     PISSN: 00144819     EISSN: None     Source Type: Journal    
DOI: 10.1007/s002210050006     Document Type: Article

References (42)

1. Andrus PK, Fleck TJ, Oostveen JA, Hall ED (1997) Neuroprotective effects of the novel brain-penetrating pyrrolopyrimidine anti-oxidants U-101033E and U-104067F against post-ischemic degeneration of nigrostriatal neurons. J Neurosci Res 47: 650-654
2. Betz AL, Randall J, Martz D (1991) Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia. Am J Physiol 260:H563-568
3. Braughler JM, Hall ED (1989) Central nervous system trauma and stroke I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free Radic Biol Med 6: 289-301
4. Cao XH, Phillis JW (1994) Alpha-phenyl-tert-butyl-nitrone reduces cortical infarct and edema in rats subjected to focal ischemia. Brain Res 644:267-272
5. Carney JM, Floyd RA (1991) Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone (PBN) and other spin-trapping agents: a novel series of nonlipid free radical scavengers. J Mol Neurosci 3:47-57
6. Chan PH (1996) Role of oxidants in ischemic brain damage. Stroke 27:1124-1129
7. Chan PH (1998) Oxygen radical mechanisms in cerebral ischemia and reperfusion. In: Hsu CY (ed) Ischemic stroke: from basic mechanisms to new drug development. Monographs in clinical neuroscience, vol 16. Karger, Basel, pp 14-27
8. Chen G, Griffin M, Poyer JL, McCay PB (1990) HPLC procedure for the pharmacokinetic study of the spin-trapping agent, alpha-phenyl-N-tert-butyl nitrone (PBN). Free Radic Biol Med 9:93-98
9. Folbergrova J, Zhao Q, Katsura K, Siesjö BK (1995) N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. Proc Natl Acad Sci USA 92:5057-5061
10. Fukuyama N, Takizawa S, Ishida H, Hoshiai K, Shinohara Y, Nakazawa H (1998) Peroxynitrite formation in focal cerebral ischemia-reperfusion in rats occurs predominantly in the periinfarct region. J Cereb Blood Flow Metab 18:123-129
11. Hall ED, Andrus PK, Smith SL, Oostveen JA, Scherch HM, Lutzke BS, Raub TJ, Sawada GA, Palmer JR, Banitt LS, Tustin JS, Belonga KL, Ayer DE, Bundy GL (1996) Neuro-protective efficacy of microvascularly-localized versus brain-penetrating antioxidants. Acta Neurochir Suppl Wien 66: 107-113
12. Hall ED, Andrus PK, Smith SL, Fleck TJ, Scherch HM, Lutzke BS, Sawada GA, Althaus JS, Vonvoigtlander PF, Padbury GE, Larson PG, Palmer JR, Bundy GL (1997) Pyrrolopyrimidines: novel brain penetrating antioxidants with neuroprotective activity in brain injury and ischemia models. J Pharmacol Exp Ther 281:895-904
13. Inanami O, Kuwabara M (1995) α-Phenyl-N-tert-butyl nitrone (PBN) increases the cortical cerebral blood flow by inhibiting the breakdown of nitric oxide in anesthetized rats. Free Radie Res 23:33-39
14. Keller JN, Kindy MS, Holtsberg FW, StClair DK, Yen HC, Germeyer A, Steiner SM, BruceKeller AJ, Hutchins JB, Mattson MP (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci 18: 687-697
15. Martz D, Beer M, Betz AL (1990) Dimethylthiourea reduces ischemic brain edema without affecting cerebral blood flow. J Cereb Blood Flow Metab 10:352-357
16. Matsumiya N, Koehler RC, Kirsch JR, Traystman RJ (1991) Conjugated Superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats. Stroke 22: 1193-1200
17. Murakami K, Kondo T, Kawase M, Li YB, Sato S, Chen SF, Chan PH (1998) Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J Neurosci 18:205-213
18. Nakai A, Kuroda S, Kristian A, Siesjö BK (1997) The immuno-suppressant drug FK506 ameliorates secondary mitochondrial dysfunction following transient focal cerebral ischemia in the rat. Neurobiol Dis 4:288-300
19. Oostveen JA, Dunn E, Carter DB, Hall ED (1998) Neuroprotective efficacy and mechanisms of novel pyrrolopyrimidine lipid peroxidation inhibitors in the gerbil forebrain ischemia model. J Cereb Blood Flow Metab 18:539-547
20. Pellegrini-Giampietro DE (1994) Free radicals and the pathogenesis of neuronal death: cooperative role of excitatory amino acids. Adv Exp Med Biol 366:59-71
21. Peters O, Back T, Lindauer U, Busch C, Megow D, Dreier J, Dirnagl U (1998) Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 18:196-205
22. Phillis JW, Clough Helfman C (1990) Protection from cerebral ischemic injury in gerbils with the spin trap agent N-tert-butyl-alpha-phenylnitrone (PBN). Neurosci Lett 116:315-319
23. Piantadosi CA, Zhang J (1996) Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke 27: 327-331
24. Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Plesnila N, Baethmann A, Reulen HJ (1997) Superior neuroprotective efficacy of a novel antioxidant (U-101033E) with improved blood-brain barrier permeability in focal cerebral ischemia. Stroke 28:2018-2024
25. Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Baethmann A, Reulen HJ (1998a) Monotherapy with dextromethorphan or tirilazad - but not a combination of both - improves outcome after transient focal cerebral ischemia in rats. Exp Brain Res 122:121-127
26. Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Baethmann A, Reulen HJ (1998b) A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage by laser Doppler flowmetry. Stroke 29:2162-2170
27. Schmid-Elsaesser R, Hungerhuber E, Zausinger S, Baethmann A, Reulen HJ (1999) Neuroprotective efficacy of combination therapy with two different antioxidants in rats subjected to transient focal ischemia. Brain Res 816:471-479
28. Schulz JB, Panahian N, Chen YI, Beal MF, Moskowitz MA, Rosen BR, Jenkins BG (1997) Facilitation of postischemic reperfusion with alpha-PBN: assessment using NMR and Doppler flow techniques. Am J Physiol 272:H1986-1995
29. Sheng H, Bart RD, Oury TD, Pearlstein RD, Crapo JD, Warner DS (1998) Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia. Neuroscience 88:185-191
30. Siesjö BK, Agardh CD, Bengtsson F (1989) Free radicals and brain damage. Cerebrovasc Brain Metab Rev 1:165-211
31. Soehle M, Heimann A, Kempski O (1998) Postischemic application of lipid peroxidation inhibitor U-101033E reduces neuronal damage after global cerebral ischemia in rats. Stroke 29: 1240-1246
32. Spranger M, Krempien S, Schwab S, Donneberg S, Hacke W (1997) Superoxide dismutase activity in serum of patients with acute cerebral ischemic injury. Correlation with clinical course and infarct size. Stroke 28:2425-2428
33. Thomas CE, Ohlweiler DF, Kalyanaraman B (1994) Multiple mechanisms for inhibition of low density lipoprotein oxidation by novel cyclic nitrone spin traps. J Biol Chem 269: 28055-28061
34. Thomas CE, Ohlweiler DF, Carr AA, Nieduzak TR, Hay DA, Adams G, Vaz R, Bernotas RC (1996) Characterization of the radical trapping activity of a novel series of cyclic nitrone spin traps. J Biol Chem 271:3097-3104
35. Thomas CE, Ohlweiler DF, Taylor VL, Schmidt CJ (1997) Radical trapping and inhibition of iron dependent CNS damage by cyclic nitrone spin traps. J Neurochem 68:1173-1182
36. Toyoda T, Lee KS (1997) Differential induction of Superoxide dismutase in core and penumbra regions after transient focal ischemia in the rat neocortex. Neurosci Lett 235:29-32
37. Traystman RJ, Kirsch JR, Koehler RC (1991) Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol 71:1185-1195
38. Wengenack TM, Curran GL, Poduslo JF (1997) Postischemic, systemic administration of polyamine-modified Superoxide dismutase reduces hippocampal CA1 neurodegeneration in rat global cerebral ischemia. Brain Res 754:46-54
39. Xiong Y, Peterson PL, Muizelaar JP, Lee CP (1997) Amelioration of mitochondrial function by a novel antioxidant U-101033E following traumatic brain injury in rats. J Neurotrauma 14: 907-917
40. Yang GY, Chan PH, Chen J, Carlson E, Chen SF, Epstein P, Kamii H (1994) Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke 25:165-170
41. Zausinger S, Hungerhuber E, Baethmann A, Reulen HJ, Schmid-Elsaesser R (1999) Neurological impairment and infarct volume after transient MCA-occlusion in the rat: a comparative study under various treatment paradigms. J Cereb Blood Flow Metab 19 (Suppl 1):S523 (abstract)
42. Zhao Q, Pahlmark K, Smith ML, Siesjö BK (1994) Delayed treatment with the spin trap α-phenyl-N-tert-butyl nitrone (PBN) reduces infarct size following transient middle cerebral artery occlusion in rats. Acta Physiol Scand 152: 349-350