title: Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury.
abstract: The therapeutic effect of a novel RNA viral vector, Sendai virus (SeV)-mediated glial cell line-derived neurotrophic factor (GDNF) gene (SeV/GDNF), on the infarct volume, was investigated after 90 minutes of transient middle cerebral artery occlusion (tMCAO) in rats with relation to nuclear translocation of apoptosis inducing factor (AIF). The topical administration of SeV/GDNF induced high level expression of GDNF protein, which effectively reduced the infarct volume when administrated 0 and 1 hours as well after the reperfusion. Twenty-four hours after ischemia, the obvious nuclear translocation of AIF was found in neurons of peri-infarct area, which significantly reduced with administration of SeV/GDNF 0 or 1 hour after reperfusion, as well as the number of TUNEL positive cells. These results demonstrate that SeV vector-mediated gene transfer of GDNF effectively reduced ischemic infarct volume after tMCAO and extended the therapeutic time window compared with previous viral vectors, and that promoting neuronal survival of GDNF might be related to the reduction of AIF nuclear translocation, indicating the high therapeutic potency of SeV/GDNF for cerebral ischemia.
authors.affiliation: Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan. ndrjin@hotmail.com
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Shoko
authors.initials: S
authors.lastname: Nagotani
authors.forename: Hanzhe
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiquan
authors.initials: X
authors.lastname: Wang
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D020520:Brain Infarction / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008297:Male; D009410:Nerve Degeneration / Q000235:genetics / Q000517:prevention & control / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D029082:Sendai virus / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051033:Apoptosis Inducing Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor