Neuroprotective Effect of N-nitro-L-arginine Methylester Pretreatment on the Early Stage of Kainic Acid Induced Neuronal Degeneration in the Rat Brain

  • Koh, Jun-Seok (Department of Neurosurgery, Hospital of Kyung-Hee University College of Medicine) ;
  • Kim, Gook-Ki (Department of Neurosurgery, Hospital of Kyung-Hee University College of Medicine) ;
  • Lim, Young-Jin (Department of Neurosurgery, Hospital of Kyung-Hee University College of Medicine) ;
  • Rhee, Bong-Arm (Department of Neurosurgery, Hospital of Kyung-Hee University College of Medicine) ;
  • Kim, Tae-Sung (Department of Neurosurgery, Hospital of Kyung-Hee University College of Medicine)
  • Published : 2005.10.28

Abstract

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

Keywords

References

  1. Bagetta G, Paoletti AM, Leta A, Del Duca C, Nistico R, Rotiroti D, et al : Abnormal expression of neuronal nitric oxide synthase triggers limbic seizures and hippocampal damage in rat. Biochem Biophys Res Commun 291 : 255-260, 2002 https://doi.org/10.1006/bbrc.2002.6424
  2. Baik EJ, Kim EJ, Lee SH, Moon C : Cyclooygenase-2 selective inhibitors aggravate kainic acid induced seizure and neuronal cell death in the hippocampus. Brain Res 843 : 118-129, 1999 https://doi.org/10.1016/S0006-8993(99)01797-7
  3. Baran H, Vass K, Lassmann H, Hornykiewicz O : The cyclooxygenase and lipoxygenase inhibitor BW-755C protect rats against kainic acidinduced seizures and neurotoxicity. Brain Res 646 : 201-206, 1994 https://doi.org/10.1016/0006-8993(94)90078-7
  4. Ben-Ari Y, Tremblay E, Riche D, Ghilini G, Naquet R : Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole : metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy. Neuroscience 6 : 1361-1391, 1981 https://doi.org/10.1016/0306-4522(81)90193-7
  5. Chen J, Marsh T, Zhang JS, Graham SH : Expression of cyclooxygenase-2 in rat brain following kainate treatment. Neuroreport 6 : 245-248, 1995
  6. Domoki F, Thrikawala N, Robins GS, Bari F, Bsuja DW : Kainic acid rapidly induces cyclooxygenase-2 in piglet cerebral cortex. Neuroreport 11 : 3435-3438, 2000 https://doi.org/10.1097/00001756-200011090-00007
  7. Forstermann U, Heldt R, Knappen F, Hertting G : Potential anticonvulsive properties of endogenous prostaglandins formed in mouse brain. Brain Res 240 : 303-310, 1982 https://doi.org/10.1016/0006-8993(82)90225-6
  8. Gallyas F, Woulff JR, Bottcher H, Zaborsky L : A reliable and sensitive method to localize terminal degeneration and lysosomes in central nervous system. Stain Technol 5 : 299-306, 1980
  9. Kanner J, Harel S, Granit R : Nitric oxide, an inhibitor of lipid oxidation by lipoxygenase and hemoglobin. Lipids 27 : 46-49, 1992 https://doi.org/10.1007/BF02537058
  10. Karthein R, Nastainczyk W, Ruf HH : EPR study of ferric native prostaglandin H synthase and its ferrous NO derivatives. Eur J Biochem 166 : 173-180, 1987 https://doi.org/10.1111/j.1432-1033.1987.tb13499.x
  11. Karyanaranman B, Mason RP, Tainer B, Eling TE : The free radical formed during the hydroperoxide deactivation of ram seminal vesicle is hemoprotein derived. J Biol Chem 257 : 4764-4768, 1982
  12. Lee JK, Kang SS, Lee MC : Stress protein expression in kainate-induced experimental temporal lobe epilepsy in rats. J Korean Neurosurg Soc 27 : 1641-1652, 1998
  13. Lees GJ : Effects of anaesthetics, anticonvulsants and glutamate antagonists on kainic acid-induced local and distal neuronal loss. J Neurol Sci 108 : 221-228, 1992 https://doi.org/10.1016/0022-510X(92)90055-P
  14. Marcheselli VL, Bazan NG : Sustained induction of prostaglandin endoperoxide-2 by seizure in hippocampus. J Biol Chem 271 : 24794- 24799, 1996 https://doi.org/10.1074/jbc.271.40.24794
  15. Miller RJ : The revenge of the kainate receptor. Trends Neurol Sci 14 : 477-479, 1991 https://doi.org/10.1016/0166-2236(91)90054-X
  16. Moncada S, Palmer RMJ, Higgs EA : Nitric oxide : Physiology, Pathophysiology and pharmacology. Pharmacol Rev 43 : 109-142, 1991
  17. Okada K, Yuhi T, Tsuji S, Yamashita U : Cyclooygenase-2 expression in the hippocampus of genetically susceptible E1 mice was increased after seizure. Brain Res 894 : 332-335, 2001 https://doi.org/10.1016/S0006-8993(01)02019-4
  18. Paoletti AM, Piccirilli S, Costa N, Rotiroti N, Bagetta G, Nistico G : Systemic administration of N-nitro-L-arginine methyl ester and indomethacin reduces the elevation of brain PGE2 content and prevents seizures and hippocampal damage evoked by LiCl and tacrine in rat. Exp Neurol 149 : 349-355, 1998 https://doi.org/10.1006/exnr.1997.6741
  19. Paxinos G, Watson C : The Rat Brain in Stereotaxic Coordinates, ed 2. Sydney : Academic Press, 1986
  20. Penix LP, Davis W, Subramaniam S : Inhibition of NO synthase increases the severity of kainic acid-induced seizure in rodents. Epilepsy Res 18 : 177-184, 1994 https://doi.org/10.1016/0920-1211(94)90038-8
  21. Rettori V, Gimeno M, Lyson K, McCann SM : Nitric oxide mediates norepinephrine-induced prostaglandin E2 release from the hypothalamus. Proc Natl Acad Sci USA 89 : 11543-11546, 1992 https://doi.org/10.1073/pnas.89.23.11543
  22. Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P : Nitric oxide activates cylooxygenase enzyme. Proc Natl Acad Sci USA 90 : 7240-7244, 1993 https://doi.org/10.1073/pnas.90.15.7240
  23. Sergei A, Forstermann U, Hertting G : Decreased levels of brain cyclooxygenase products as a possible cause of increased seizure susceptibility in convulsion-prone gerbils. Brain Res 305 : 393-395, 1984 https://doi.org/10.1016/0006-8993(84)90450-5
  24. Swierkosz TA, Mitchell J, Warner TD, Botting RM, Vane JR : Co-induction of nitric oxide synthase and cyclooxygenase : interactions between nitric oxide and prostanoids. Br J Pharmacol 114 : 1335- 1342, 1995 https://doi.org/10.1111/j.1476-5381.1995.tb13353.x
  25. Tanaka K, Graham SH, Simon RP : The role of excitatory neurotransmitter in seizure-induced neuronal injury in rats. Brain Res 737 : 59-63, 1996 https://doi.org/10.1016/0006-8993(96)00658-0
  26. Urbanska EM, Drelewska E, Borowicz KK, Blaszczak P, Kleinrok Z, Czuczwar SZ : N-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice. J Neural Transm 103 : 1145-1152, 1996 https://doi.org/10.1007/BF01271199
  27. Yamagata K, Abdreasson KI, Kauffmann WE, Barnes CA, Worley PF : Expression of mitogen-inducible cyclooxygenase in brain neurons : regulation by synaptic activity and glucocorticoids. Neuron 11 : 371- 386, 1993 https://doi.org/10.1016/0896-6273(93)90192-T