The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

  • Byun, Jong-Seon (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lee, Sang-Hyun (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Jeon, Seong-Ho (Department of Pharmacology, College of Pharmacy, Kangwon National University) ;
  • Kwon, Yong-Soo (Department of Pharmacology, College of Pharmacy, Kangwon National University) ;
  • Lee, Hee-Jae (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Young-Myeong (Department of Molecular and Cellular Biochemistry, College of Medicine, Kangwon National University) ;
  • Kim, Myong-Jo (Division of Bio-resources Technology, Kangwon National University) ;
  • Chun, Wan-Joo (Department of Pharmacology, College of Medicine, Kangwon National University)
  • Published : 2009.08.31
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Abstract

Nitric oxide (NO) has both neuroprotective and neurotoxic effects depending on its concentration and the experimental model. We tested the effects of NG-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a selective inducible NOS (iNOS) inhibitor, on kainic acid (KA)-induced seizures and hippocampal CA3 neuronal death. L-NAME (50 mg/kg, i.p.) and/or aminoguanidine (200 mg/kg, i.p.) were administered 1 h prior to the intracerebroventricular (i.c.v.) injection of KA. Pretreatment with L-NAME significantly increased KA-induced CA3 neuronal death, iNOS expression, and activation of microglia. However, pretreatment with aminoguanidine significantly suppressed both the KA-induced and L-NAME-aggravated hippocampal CA3 neuronal death with concomitant decreases in iNOS expression and microglial activation. The protective effect of aminoguanidine was maintained for up to 2 weeks. Furthermore, iNOS knockout mice ($iNOS^{-1-}$) were resistant to KA-induced neuronal death. The present study demonstrates that aminoguanidine attenuates KA-induced neuronal death, whereas L-NAME aggravates neuronal death, in the CA3 region of the hippocampus, suggesting that NOS isoforms play different roles in KA-induced excitotoxicity.

Keywords

References

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