Science Links Japan | Sendai Virus Vector-mediated Gene Transfer of Glial Cell Line-Derived Neurotrophic Factor Prevents Delayed Neuronal Death after Transient Global Ischemia in Gerbils.

Sendai Virus Vector-mediated Gene Transfer of Glial Cell Line-Derived Neurotrophic Factor Prevents Delayed Neuronal Death after Transient Global Ischemia in Gerbils.

Accession number;03A0376728

Title;Sendai Virus Vector-mediated Gene Transfer of Glial Cell Line-Derived Neurotrophic Factor Prevents Delayed Neuronal Death after Transient Global Ischemia in Gerbils.

Author; SHIRAKURA M (Dnavec Res. Inc., Ibaraki, Jpn) FUKUMURA M (Dnavec Res. Inc., Ibaraki, Jpn) INOUE M (Dnavec Res. Inc., Ibaraki, Jpn) FUJIKAWA S (Dnavec Res. Inc., Ibaraki, Jpn) MAEDA M (Osaka City Univ. Medical School, Osaka, Jpn) WATABE K (Tokyo Metropolitan Inst. Neurosci., Tokyo, Jpn) KYUWA S (Univ. Tokyo, Tokyo, Jpn) YOSHIKAWA Y (Univ. Tokyo, Tokyo, Jpn) HASEGAWA M (Dnavec Res. Inc., Ibaraki, Jpn)

Journal Title;Exp Anim

Journal Code:Z0755A

ISSN:1341-1357

VOL.52;NO.2;PAGE.119-127(2003)

Figure&Table&Reference;FIG.6, REF.31

Pub. Country;Japan

Language;English

Abstract;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. (author abst.)

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