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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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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