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Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils

Gene Therapy volume 11, pages 784–790 (2004)Cite this article

Abstract

Sendai virus (SeV) vector-mediated gene delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) prevented the delayed neuronal death induced by transient global ischemia in gerbils, even when the vector was administered several hours after ischemia. Intraventricular administration of SeV vector directed high-level expression of the vector-encoded neurotrophic factor genes, which are potent candidates for the treatment of neurodegenerative diseases. After occlusion of the bilateral carotid arteries of gerbils, SeV vector carrying GDNF (SeV/GDNF), NGF (SeV/NGF), brain-derived neurotrophic factor (SeV/BDNF), insulin-like growth factor-1 (SeV/IGF-1) or vascular endothelial growth factor (SeV/VEGF) was injected into the lateral ventricle. Administration of SeV/GDNF, SeV/NGF or SeV/BDNF 30 min after the ischemic insult effectively prevented the delayed neuronal death of the hippocampal CA1 pyramidal neurons. Furthermore, the administration of SeV/GDNF or SeV/NGF as late as 4 or 6 h after the ischemic insult also prevented the death of these neurons. These results indicate that SeV vector-mediated gene transfer of neurotrophic factors has high therapeutic potency for preventing the delayed neuronal death induced by transient global ischemia, and provides an approach for gene therapy of stroke.

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Acknowledgements

We thank T Yamamoto for technical assistance, and A Iida, M Okayama and M Fukumura for helpful discussions.

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Authors and Affiliations

  1. DNAVEC Research Inc., Tsukuba, Japan

    M Shirakura, M Inoue, S Fujikawa, K Washizawa, S Komaba & M Hasegawa

  2. Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan

    M Shirakura & Y Yoshikawa

  3. First Department of Anatomy, Osaka City University Medical School, Osaka, Japan

    M Maeda

  4. Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan

    K Watabe

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Shirakura, M., Inoue, M., Fujikawa, S. et al. Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils. Gene Ther 11, 784–790 (2004). https://doi.org/10.1038/sj.gt.3302224

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  • DOI: https://doi.org/10.1038/sj.gt.3302224

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