Korean J Physiol Pharmacol.  2009 Aug;13(4):265-271. 10.4196/kjpp.2009.13.4.265.

Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

Affiliations
  • 1Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea. wchun@kangwon.ac.kr
  • 2Department of Pharmacology, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea.
  • 3Department of Molecular and Cellular Biochemistry, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
  • 4Division of Bio-resources Technology, Kangwon National University, Chuncheon 200-701, Korea.

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-/-) 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.

Keyword

Kainic acid; Nitric oxide; L-NAME; Aminoguanidine; iNOS; Neuronal death
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