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Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia

Gene Therapy volume 12, pages 487–493 (2005)Cite this article

Abstract

Gene therapy may be a promising approach for treatment of brain ischemia. In this study, we examined the effect of postischemic gene transfer of midkine, a heparin-binding neurotrophic factor, using a focal brain ischemia model with the photothrombotic occlusion method. At 90 min after induction of brain ischemia in spontaneously hypertensive rats, a replication-deficient recombinant adenovirus encoding mouse midkine (AdMK, n=7) or a control vector encoding β-galactosidase (Adβgal, n=7) was injected into the lateral ventricle ipsilateral to ischemia. At 2 days after ischemia, we determined infarct volume by 2,3,5-triphenyltetrazolium chloride staining. There were no significant differences in cerebral blood flow 1 h after ischemia between AdMK and Adβgal groups. Infarct volume of AdMK group was 51±27 mm3, which was significantly smaller than that of Adβgal group (86±27 mm3, P<0.05). TUNEL-positive and cleaved caspase-3-positive cells in the periischemic area of AdMK-treated rats were significantly fewer than those in Adβgal-treated rats, suggesting that the reduction of infarct volume by midkine was partly mediated by its antiapoptotic action. Thus, gene transfer of midkine to the ischemic brain may be effective in the treatment of brain ischemia.

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Acknowledgements

This work was supported in part by the research grant in aid from the Ministry of Health and Welfare Comprehensive Research on Aging and Health (H11-008), Japan and from the Ministry of Education, Science and Culture (14570604), Japan (HO). We would like to thank the University of Iowa Gene Transfer Vector Core, especially Maria Scheel, Kate Lamsey and Beverly L Davidson, for viral vector preparations.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    J Takada, H Ooboshi, T Ago, T Kitazono, H Yao, S Ibayashi & M Iida

  2. Department of Biochemistry, Nagoya University School of Medicine, Nagoya, Japan

    K Kadomatsu & T Muramatsu

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  1. J Takada
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  2. H Ooboshi
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Takada, J., Ooboshi, H., Ago, T. et al. Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia. Gene Ther 12, 487–493 (2005). https://doi.org/10.1038/sj.gt.3302434

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