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Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons

Gene Therapy volume 8, pages 1167–1173 (2001)Cite this article

Abstract

To develop a novel strategy to prevent delayed neuronal death (DND) following transient occlusion of arteries, the gene of hepatocyte growth factor (HGF), a novel neurotrophic factor, was transfected into the subarachnoid space of gerbils after transient forebrain ischemia. Importantly, transfection of HGF gene into the subarachnoid space prevented DND, accompanied by a significant increase in HGF in the cerebrospinal fluid. Prevention of DND by HGF is due to the inhibition of apoptosis through the blockade of bax translocation from the cytoplasm to the nucleus. HGF gene transfer into the subarachnoid space may provide a new therapeutic strategy for cerebrovascular disease.

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Acknowledgements

We wish to thank Rie Kosai and Keiko Yamaguchi for their excellent technical assistance. This work was partially supported by grants from the Japan Health Sciences Foundation, and the Japan Cardiovascular Research Foundation, a Japan Heart Foundation Research Grant, a Grant-in-Aid from the Japan Society for the Promotion of Science, the Ministry of Education, Science, Sports and Culture, and Ministry of Public Health.

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Authors and Affiliations

  1. Department of Neurosurgery, Gifu University School of Medicine, Gifu, Japan

    K Hayashi, S Yoshimura & N Sakai

  2. Department of Pathology, Gifu University School of Medicine, Gifu, Japan

    A Hara

  3. Division of Gene Therapy Science, Biomedical Research Center, Graduate School of Medicine, Osaka University, Suita, Japan

    R Morishita, T Ogihara & Y Kaneda

  4. Department of Geriatric Medicine, Biomedical Research Center, Graduate School of Medicine, Osaka University, Suita, Japan

    R Morishita & H Nakagami

  5. Division of Biochemistry, Biomedical Research Center, Graduate School of Medicine, Osaka University, Suita, Japan

    K Matsumoto & T Nakamura

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  1. K Hayashi
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Hayashi, K., Morishita, R., Nakagami, H. et al. Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons. Gene Ther 8, 1167–1173 (2001). https://doi.org/10.1038/sj.gt.3301498

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  • DOI: https://doi.org/10.1038/sj.gt.3301498

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