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Immunohistochemical Study on Distribution of NF-κB and p53 in Gerbil Hippocampus after Transient Cerebral Ischemia: Effect of Pitavastatin

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We investigated the immunohistochemical alterations of the transcription nuclear factor kappa-B (NF-κB) and transcription factor p53 in the hippocampus after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of NF-κB, p53 and neuronal nuclei in the hippocampus after ischemia. Severe neuronal damage was observed in the hippocampal CA1 neurons 5 and 14 days after ischemia. In the present study, the increase of NF-κB immunoreactivity in glial cells and p53 immunoreactivity in neurons preceded neuronal damage in the hippocampal CA1 sector after ischemia. Thereafter, NF-κB immunoreactivity was induced highly in reactive astrocytes and microglia of the hippocampal CA1 sector where severe neuronal damage was observed. Our immunohistochemical study showed that pitavastatin prevented the alterations of NF-κB and p53 in the hippocampal CA1 sector 5 days after transient ischemia. Furthermore, our results with neuronal nuclei immunostaining indicate that pitavastatin dose-dependently prevented the neuronal cell death in the hippocampal CA1 sector 5 days after transient cerebral ischemia. These results suggest that the up-regulations of NF-κB in glia and p53 in neurons can cause neuronal cell death after ischemia. Our findings also support the hypothesis that NF-κB- and/or p53-mediated neuronal cell death is prevented through decreasing oxidative stress by pitavastatin. Thus, NF-κB and p53 may provide an attractive target for the development of novel therapeutic approaches for brain stroke.

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Acknowledgments

The authors appreciatively acknowledge Kowa Company, Ltd., Tokyo, Japan, for providing pitavastatin, and helpful advice. This study was supported in part by the Grant-in-Aid for Scientific Research (12877163, 13671095 and 13670627) from the Ministry of Science and Education in Japan.

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Authors and Affiliations

  1. Department of Drug Metabolism and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima, 770-8505, Japan

    Hiroko Tounai, Natsumi Hayakawa & Tsutomu Araki

  2. Department of Neurology, Organized Center of Clinical Medicine, International University of Health and Welfare, Tochigi, Japan

    Hiroyuki Kato

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  1. Hiroko Tounai
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  2. Natsumi Hayakawa
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  4. Tsutomu Araki
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Correspondence to Tsutomu Araki.

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Hiroko Tounai and Natsumi Hayakawa equally contributed.

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Tounai, H., Hayakawa, N., Kato, H. et al. Immunohistochemical Study on Distribution of NF-κB and p53 in Gerbil Hippocampus after Transient Cerebral Ischemia: Effect of Pitavastatin. Metab Brain Dis 22, 89–104 (2007). https://doi.org/10.1007/s11011-006-9040-3

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