Post-ischemic administeration but not pre-ischemic administeration of N G -nitro-L-arginine prevents spatial memory impairments and apoptosis by an inhibition of a delayed increase in NO x - in the hippocampus following repeated cerebral ischemia

K. Mishima, F. Pu, T. Kaneko, Nobuaki Egashira, K. Iwasaki, M. Fujiwara

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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.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalNeuropharmacology
Volume44
Issue number4
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

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Brain Ischemia
Arginine
Hippocampus
Ischemia
Apoptosis
NG-Nitroarginine Methyl Ester
Mortality
Nitric Oxide Synthase
Reperfusion
Spatial Memory
Inhibition (Psychology)

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

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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.",
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AU - Pu, F.

AU - Kaneko, T.

AU - Egashira, Nobuaki

AU - Iwasaki, K.

AU - Fujiwara, M.

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