The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Postischemic Treatment with Aminoguanidine Inhibits Peroxynitrite Production in the Rat Hippocampus Following Transient Forebrain Ischemia

  • Choi, Yun-Sik (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Yeo-Hong (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Lee, Ju-Eun (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Cho, Kyung-Ok (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Seong-Yun (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sang-Bok (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
  • Published : 2004.02.21
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Abstract

Transient forebrain ischemia results in the delayed neuronal death in the CA1 area of the hippo-campus. The present study was performed to determine effects of aminoguanidine, a selective iNOS inhibitor, on the generation of peroxynitrite and delayed neuronal death occurring in the hippocampus following transient forebrain ischemia. Transient forebrain ischemia was produced in the conscious rats by four-vessel occlusion for 10 min. Treatment with aminoguanidine (100 mg/kg or 200 mg/kg, i.p.) or saline (0.4 ml/100 g, i.p.) was started 30 min following ischemia-reperfusion and the animals were then injected twice daily until 12 h before sacrifice. Immunohistochemical method was used to detect 3-nitrotyrosine, a marker of peroxynitrite production. Posttreatment of aminoguanidine (200 mg/kg) significantly attenuated the neuronal death in the hippocampal CA1 area 3 days, but not 7 days, after ischemia-reperfusion. 3-Nitrotyrosine immunoreactivity was enhanced in the hippocampal CA1 area 3 days after reperfusion, which was prevented by the treatment of aminoguanidine (100 mg/kg and 200 mg/kg). Our findings showed that (1) the generation of peroxynitrite in the hippocampal CA1 area 3 days after ischemia-reperfusion was dependent on the iNOS activity; (2) the postischemic delayed neuronal death was attenuated in the early phase through the prevention of peroxynitrite generation by an iNOS inhibitor.

Keywords

References

  1. Alps BJ, Hass WK. The potential beneficial effect of nicardipine in a rat model of transient forebrain ischemia. Neurology 37:809-814, 1987 https://doi.org/10.1212/WNL.37.5.809
  2. Beckman JS, Beckman TW, Chen J, Marshall PA, Freedman B. Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc Soc Natl Acad Sci 87: 1620-1624, 1990 https://doi.org/10.1073/pnas.87.4.1620
  3. Chalimoniuk M, Strosznajder J. NMDA receptor-dependent nitric oxide and cGMP synthesis in brain hemispheres and cerebellum during reperfusion after transient forebrain ischemia in gerbils: effect of 7-nitroindazole. J Neurosci Res 54: 681-690, 1998 https://doi.org/10.1002/(SICI)1097-4547(19981201)54:5<681::AID-JNR13>3.0.CO;2-L
  4. Choi DW. Cerebral hypoxia: Some new approaches and unanswered questions. J Neurosci 10: 2493-2501, 1990
  5. Choi YS, Lee MY, Sung KW, Jeong SW, Choi JS, Park HJ, Kim ON, Lee SB, Kim SY. Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol Cells 16(2): 232-238, 2003
  6. Deshpande JK, Siesjo BK, Wieloch T. Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia. J Cereb Blood Flow Metab 7: 89-95, 1987 https://doi.org/10.1038/jcbfm.1987.13
  7. Fassbender K, Fatar M, Ragoschke A, Picard M, Bertsch T, Kuehl S, Hennerici M. Subacute but not acute generation of nitric oxide in focal cerebral ischemia. Stroke 31: 2208-2211, 2000 https://doi.org/10.1161/01.STR.31.9.2208
  8. Hansen AJ. Effect of anoxia on ion distribution in the brain. Physiol Rev 65: 101-148, 1985 https://doi.org/10.1152/physrev.1985.65.1.101
  9. Hossmann K-A. Viability thresholds and the penumbra of focal ischemia. Ann Neurol 36: 557-565, 1994 https://doi.org/10.1002/ana.410360404
  10. Iadecola C. Bright and dark sides of nitric oxide in ischemic brain damage. Trends Neurosci 20: 132-138, 1997 https://doi.org/10.1016/S0166-2236(96)10074-6
  11. Iadecola C, Zhang F, Xu X. Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am J Physiol 268: R286-R292, 1995
  12. Kader A, Frazzini VI, Solomon RA, Trifiletti RR. Nitric oxide production during focal cerebral ischemia in rats. Stroke 24: 1709-1716, 1993 https://doi.org/10.1161/01.STR.24.11.1709
  13. Kim HJ, Kim SY. Increase of peroxynitrite production in the rat brain following transient forebrain ischemia. Kor J Physiol Pharmacol 5: 205-212, 2001
  14. Kinouchi H, Epstein CJ, Mizui T, Carlson E, Chen SF, Chan PH. Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc Natl Acad Sci USA 88: 11158-11162, 1991 https://doi.org/10.1073/pnas.88.24.11158
  15. Kirino T, Tamura A, Sano K. A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17: 455-459, 1986 https://doi.org/10.1161/01.STR.17.3.455
  16. Kirsch JR, Bhardwaj A, Martin LJ, Hanley DF, Traystman RJ. Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats. Stroke 28: 2259-2264, 1997 https://doi.org/10.1161/01.STR.28.11.2259
  17. Kondo T, Reaume AG, Huang T-T, Carlson E, Murakami K, Chen SF, Hoffman EK, Scott RW, Epstein CJ, Chan PH. Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J Neurosci 17: 4180-4189, 1997
  18. Kumura E, Yoshimine T, Iwatsuka K-I, Yamanaka K, Tanaka S, Hayakawa T, Shiga T, Kosaka H. Generation of nitric oxide and superoxide during reperfusion after focal cerebral ischemia in rats. Am J Physiol 270: C748-C752, 1996 https://doi.org/10.1152/ajpcell.1996.270.3.C748
  19. Kuo PC, Schroeder JS. The emerging multifaceted roles of nitric oxide. Ann Surgery 221: 220-235, 1995 https://doi.org/10.1097/00000658-199503000-00003
  20. Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors for ischemic stroke. Stroke 34(10): 2518-2532, 2003 https://doi.org/10.1161/01.STR.0000089015.51603.CC
  21. Mori K, Togashi H, Ueno KI, Matsumoto M, Yoshioka M. Aminoguanidine prevented the impairment of learning behavior and hippocampal long-term potentiation following transient cerebral ischemia. Behav Brain Res 120: 159-168, 2001 https://doi.org/10.1016/S0166-4328(00)00371-5
  22. Nagayama M, Zhang F, Iadecola C. Delayed treatment with aminoguanidine decreases focal cerebral ischemic damage and enhances neurologic recovery in rats. J Cereb Blood flow Metab 18: 1107-1113, 1998 https://doi.org/10.1097/00004647-199810000-00007
  23. Nanri K, MontecotC, Springhetti V, Seylaz J, Pinard E. The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats. Stroke 29: 1248-1253, 1998 https://doi.org/10.1161/01.STR.29.6.1248
  24. Niwa K, Takizawa S, Kawaguchi C, Kamiya U, Kuwahira I, Shinohara Y. Expression of inducible nitric oxide synthase immunoreactivity in rat brain following chronic hypoxia: effect of aminoguanidine. Neurosci Lett 271: 109-112, 1999 https://doi.org/10.1016/S0304-3940(99)00534-0
  25. Olanow CW. A radical hypothesis for neurodegeneration. Trends Neurosci 16: 439-444, 1993 https://doi.org/10.1016/0166-2236(93)90070-3
  26. Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10: 267-272, 1979 https://doi.org/10.1161/01.STR.10.3.267
  27. Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11: 491-498, 1982 https://doi.org/10.1002/ana.410110509
  28. Samdeni AF, Dawson TM, Dawson VL. Nitric oxide synthase in models of focal ischemia. Stroke 28: 1283-1288, 1997 https://doi.org/10.1161/01.STR.28.6.1283
  29. Szabo C. The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6: 79-88, 1996 https://doi.org/10.1097/00024382-199608000-00001
  30. Veltkamp R, Rajapakse N, Robins G, Puskar M, Shimizu K, Busija D. Transient focal ischemia increases endothelial nitric oxide synthase in cerebral blood vessels. Stroke 33(11): 2704-2710, 2002 https://doi.org/10.1161/01.STR.0000033132.85123.6A
  31. Villa P, Bigini P, Mennini T, Agnello D, Laragione T, Cagnotto A, Viviani B, Marinovich M, Cerami A, Coleman TR, Brines M, Ghezzi P. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 198(6): 971-975, 2003 https://doi.org/10.1084/jem.20021067
  32. Zhang J, Benveniste H, Klitzman B, Piantadosi CA. Nitric oxide synthase inhibition and extracellular glutamate concentration after cerebral ischemia/reperfusion. Stroke 26: 298-304, 1995 https://doi.org/10.1161/01.STR.26.2.298