Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus.
10.4196/kjpp.2009.13.4.265
- Author:
Jong Seon BYUN
1
;
Sang Hyun LEE
;
Seong Ho JEON
;
Yong Soo KWON
;
Hee Jae LEE
;
Sung Soo KIM
;
Young Myeong KIM
;
Myong Jo KIM
;
Wanjoo CHUN
Author Information
1. Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea. wchun@kangwon.ac.kr
- Publication Type:Original Article
- Keywords:
Kainic acid;
Nitric oxide;
L-NAME;
Aminoguanidine;
iNOS;
Neuronal death
- MeSH:
Animals;
Guanidines;
Hippocampus;
Kainic Acid;
Mice;
Mice, Knockout;
Microglia;
Models, Theoretical;
Neurons;
NG-Nitroarginine Methyl Ester;
Nitric Oxide;
Nitric Oxide Synthase;
Protein Isoforms;
Seizures
- From:The Korean Journal of Physiology and Pharmacology
2009;13(4):265-271
- CountryRepublic of Korea
- Language:English
-
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.
