title: Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Jong-Seon
authors.initials: JS
authors.lastname: Byun
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Jeon
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Myong-Jo
authors.initials: MJ
authors.lastname: Kim
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun