Brain dysfunction associated with an induction of nitric oxide synthase following an intracerebral injection of lipopolysaccharide in rats

K. Yamada, Y. Komori, T. Tanaka, K. Senzaki, T. Nikai, H. Sugihara, T. Kameyama, T. Nabeshima

研究成果: Article

69 引用 (Scopus)

抄録

We investigated the pathophysiological role of nitric oxide synthesized by inducible nitric oxide synthase in the brain, by injecting lipopolysaccharide directly into the rat cerebral cortex/hippocampus. The levels of nitric oxide metabolites, nitrite and nitrate, began to increase in a dose-dependent manner with a 3-h lag, and reached approximately seven-fold the basal levels 8 h after the direct injection of lipopolysaccharide (5 μg). The lipopolysaccharide-induced increase in nitrite and nitrate levels was inhibited by treatment with the specific inducible nitric oxide synthase inhibitor aminoguanidine. The protein synthesis inhibitor cycloheximide delayed the onset of the increase in nitric oxide metabolite levels, and reduced the peak levels. Lipopolysaccharide increased Ca2+-independent, but not Ca2+-dependent, nitric oxide synthase activity in the brain. Intense nicotinamide adenine dinucleotide phosphate-diaphorase activity was observed in round cells in the vicinity of the site of injection of lipopolysaccharide 8 h after the injection. Neuronal death was observed seven days after the injection of lipopolysaccharide. Spatial memory, as assessed by performance in a water maze task and spontaneous alternation behavior in a Y-maze, was significantly impaired in rats which had had previous bilateral injections of lipopolysaccharide into the hippocampus. The lipopolysaccharide-induced neuronal death and spatial memory impairments were prevented by aminoguanidine. These results suggest that direct injection of lipopolysaccharide into the brain causes an induction of inducible nitric oxide synthase in vivo. Furthermore, it is suggested that nitric oxide produced by inducible nitric oxide synthase is responsible for the lipopolysaccharide-induced brain dysfunction.

元の言語English
ページ(範囲)281-294
ページ数14
ジャーナルNeuroscience
88
発行部数1
DOI
出版物ステータスPublished - 01-01-1999
外部発表Yes

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Nitric Oxide Synthase
Lipopolysaccharides
Injections
Brain
Nitric Oxide Synthase Type II
Nitric Oxide
Nitrites
Nitrates
Hippocampus
Protein Synthesis Inhibitors
Cycloheximide
NADP
Cerebral Cortex
Water

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Yamada, K. ; Komori, Y. ; Tanaka, T. ; Senzaki, K. ; Nikai, T. ; Sugihara, H. ; Kameyama, T. ; Nabeshima, T. / Brain dysfunction associated with an induction of nitric oxide synthase following an intracerebral injection of lipopolysaccharide in rats. :: Neuroscience. 1999 ; 巻 88, 番号 1. pp. 281-294.
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Brain dysfunction associated with an induction of nitric oxide synthase following an intracerebral injection of lipopolysaccharide in rats. / Yamada, K.; Komori, Y.; Tanaka, T.; Senzaki, K.; Nikai, T.; Sugihara, H.; Kameyama, T.; Nabeshima, T.

:: Neuroscience, 巻 88, 番号 1, 01.01.1999, p. 281-294.

研究成果: Article

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AU - Yamada, K.

AU - Komori, Y.

AU - Tanaka, T.

AU - Senzaki, K.

AU - Nikai, T.

AU - Sugihara, H.

AU - Kameyama, T.

AU - Nabeshima, T.

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