Nitric oxide synthase inhibitors L-NAME and 7-nitroindazole protect rat hippocampus against kainate-induced excitotoxicity.
The role of nitric oxide in cerebral insults remains controversial. While numerous studies have used models of ischaemia and hypoxia, few have examined nitric oxide in the kainate model of excitotoxicity. Kainate (10 mg/kg) was administered to rats via the intraperitoneal (i.p.) route to induce submaximal damage to the CA1, CA2 and CA3a regions of the hippocampus after 7 days. Systemic injections of the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), both at a dose of 5 mg/kg, reduced cell death in all three regions. As 7-NI selectively inhibits the neuronal form of NOS, this study suggests that nitric oxide produced from a neuronal and not epithelial source may contribute to neuronal damage in this model.
Jones
P A
PA
Institute of Biomedical and Life Sciences, University of Glasgow, UK.
Smith
R A
RA
Stone
T W
TW
D000704:Analysis of Variance; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007191:Indazoles / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D007191:Indazoles; D009498:Neurotoxins; D019001:Nitric Oxide Synthase; D007608:Kainic Acid; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester