Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury.
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.
Jin
Guang
G
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan. ndrjin@hotmail.com
Inoue
Makoto
M
Hayashi
Takeshi
T
Deguchi
Kentaro
K
Nagotani
Shoko
S
Zhang
Hanzhe
H
Wang
Xiquan
X
Shoji
Mikio
M
Hasegawa
Mamoru
M
Abe
Koji
K
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
D051033:Apoptosis Inducing Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor