J Korean Neurosurg Soc.  2005 Oct;38(4):287-292.

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

• Koh JS
• Kim GK
• Lim YJ
• Rhee BA
• Kim TS

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.

Keyword

Cyclooxygenase-2(COX-2); Kainic acid; Neurodegeneration; Nitric oxide(NO); N-nitro-L-arginine methyl ester(L-NAME)

MeSH Terms

Amygdala
Animals
Brain*
Dentate Gyrus
Hippocampus
Kainic Acid*
Neurons*
Neuroprotective Agents*
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Prosencephalon
Prostaglandin-Endoperoxide Synthases
Rats*
Seizures
Silver
Kainic Acid
NG-Nitroarginine Methyl Ester
Neuroprotective Agents
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
Silver