Sendai Virus Vecto-mediated Gene Transfer of Glial Cell Line-Derived Nertotrophic Factor Prevents Delayed Neuronal Death after Transient Global Ischemia in Gerbils
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概要
- 論文の詳細を見る
We have developed a cytoplasmic replicating virus vector of Sendai virus (SeV) that infects and replicates in most mammalian cells, including neurons, and directs high-level gene expression. To investigate the protective effect of SeV vector-mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) on the delayed neuronal death caused by transient global ischemia in gerbils, SeV vectors carrying either GDNF (SeV/GDNF) or enhanced green fluorescent protein gene (SeV/GFP) were stereotaxically microinjected into the lateral ventricle. Four days after injection, occlusion of the bilateral common carotid arteries for 5 min produced transient global forebrain ischemia. Treatment with SeV/GDNF significantly decreased the delayed neuronal death of the hippocampal CA1 pyramidal neurons observed 6 days after the operation. TUNEL staining demonstrated that SeV/GDNF treatment markedly reduced the number of apoptotic cells in the hippocampal CA1 neurons, indicating that SeV/GDNF treatment prevented apoptosis. Furthermore, delayed neuronal death on the contralateral side of the hippocampal CA1 was also prevented to a similar extent as that on the ipsilateral side. These results suggest that SeV/GDNF prevents the delayed neuronal death induced by ischemia and is potentially useful for gene therapy for stroke.
- 2003-04-01
著者
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KYUWA Shigeru
Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University
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YOSHIKAWA Yasuhiro
Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University
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Kyuwa Shigeru
Department Of Biomedical Science Graduate School Of Agricultural And Life Science The University Of
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Maeda Mitsuyo
First Department Of Anatomy Osaka City University Medical School
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INOUE Makoto
DNAVEC Corporation
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HASEGAWA Mamoru
DNAVEC Corporation
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WATABE Kazuhiko
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience
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Kyuwa Shigeru
Department Of Animal Pathology Institute Of Medical Science University Of Tokyo
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SHIRAKURA Masayuki
DNAVEC Research Inc.
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FUKUMURA Masayuki
DNAVEC Research Inc.
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FUJIKAWA Satoshi
DNAVEC Research Inc.
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Yoshikawa Yasuhiro
Department Of Biomedical Science Graduate School Of Agricultural And Life Science The University Of
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Yoshikawa Yasuhiro
Department Of Biomedical Science Faculty Of Agriculture The University Of Tokyo
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Watabe Kazuhiko
Department Of Molecular Neuropatholgy Tokyo Metropolitan Institute For Neurosience
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Watabe Kazuhiko
Department Of Chemistry Faculty Of Science Kanazawa University
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Inoue Makoto
Dnavec Research Inc.
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