Abstract
The therapeutic effect of a novel RNA viral vector, Sendai virus (SeV)-mediated glial cell line-derived neurotrophic factor (GDNF) gene (SeV/CDNF), 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/CDNF 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/CDNF 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.
| Original language | English |
|---|---|
| Pages (from-to) | 731-739 |
| Number of pages | 9 |
| Journal | Neurological Research |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Sep 2008 |
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Keywords
- Apoptosis inducing factor
- Focal cerebral ischemia
- Glial cell line-derived neurotrophic factor
- Sendai virus vector
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
Cite this
Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury. / Jin, Guang; Inoue, Makoto; Hayashi, Takeshi; Deguchi, Kentaro; Nagotani, Shoko; Zhang, Hanzhe; Wang, Xiquan; Shoji, Mikio; Hasegawa, Mamoru; Abe, Koji.
In: Neurological Research, Vol. 30, No. 7, 09.2008, p. 731-739.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury
AU - Jin, Guang
AU - Inoue, Makoto
AU - Hayashi, Takeshi
AU - Deguchi, Kentaro
AU - Nagotani, Shoko
AU - Zhang, Hanzhe
AU - Wang, Xiquan
AU - Shoji, Mikio
AU - Hasegawa, Mamoru
AU - Abe, Koji
PY - 2008/9
Y1 - 2008/9
N2 - The therapeutic effect of a novel RNA viral vector, Sendai virus (SeV)-mediated glial cell line-derived neurotrophic factor (GDNF) gene (SeV/CDNF), 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/CDNF 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/CDNF 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.
AB - The therapeutic effect of a novel RNA viral vector, Sendai virus (SeV)-mediated glial cell line-derived neurotrophic factor (GDNF) gene (SeV/CDNF), 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/CDNF 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/CDNF 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.
KW - Apoptosis inducing factor
KW - Focal cerebral ischemia
KW - Glial cell line-derived neurotrophic factor
KW - Sendai virus vector
UR - http://www.scopus.com/inward/record.url?scp=51649112434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51649112434&partnerID=8YFLogxK
U2 - 10.1179/174313208X305418
DO - 10.1179/174313208X305418
M3 - Article
C2 - 18593521
AN - SCOPUS:51649112434
VL - 30
SP - 731
EP - 739
JO - Neurological Research
JF - Neurological Research
SN - 0161-6412
IS - 7
ER -