Post-ischemic administration [correction of administeration] but not pre-ischemic administration [correction of administeration] of NG-nitro-L-arginine prevents spatial memory impairments and apoptosis by an inhibition of a delayed increase in NOx- in the hippocampus following repeated cerebral ischemia.

Abstract

In the present study, we investigated the effects of N(G)-nitro-L-arginine (L-NAME), an inhibitor of nitric oxide synthase, on repeated cerebral ischemia-induced impairment of spatial memory of the 8-arm radial maze in rats. Repeated ischemia (10 min ischemia x 2 times with 1 h interval) impaired the spatial memory in the 8-arm radial maze test and produced apoptosis in the hippocampus 7 days after final occlusion, and gradually increased the NO(x)(-) levels approximately 30-180 min after the second reperfusion. Post-ischemic administration of L-NAME at a dose of 50 mg/kg, i.p. 30 min following the second occlusion, significantly attenuated the repeated ischemia-induced impairment of spatial memory in the 8-arm radial maze test and suppressed apoptosis in the hippocampus, and also significantly suppressed a delayed increase in the NO(x)(-) levels induced by repeated ischemia. However, pre-ischemic administration of L-NAME at a dose of 50 mg/kg, i.p. 30 min before the first occlusion, caused about 90% mortality (the mortality rate of vehicle-treated group was 10%). These results suggest that the delayed generation of NO(x)(-) may cause spatial memory impairment and induction of apoptosis in the hippocampus in rats subjected to repeated ischemia.

• Authors: K Mishima, F Pu, T Kaneko, N Egashira, K Iwasaki, M Fujiwara
• Journal: Neuropharmacology (Neuropharmacology) Vol. 44 Issue 4 Pg. 533-40 (Mar 2003) ISSN: 0028-3908 [Print] England
• PMID: 12646290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Nitroarginine
• Nitric Oxide
• Nitric Oxide Synthase

Topics

• Animals
• Apoptosis (drug effects)
• Brain Ischemia (metabolism, pathology, psychology)
• Disease Models, Animal
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Hippocampus (blood supply, drug effects, metabolism, pathology)
• Injections, Intraperitoneal
• Injections, Intraventricular
• Maze Learning (drug effects)
• Memory (drug effects)
• Microdialysis
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitroarginine (administration & dosage, pharmacology)
• Rats
• Rats, Wistar
• Time Factors