Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury

Guang Jin, Makoto Inoue, Takeshi Hayashi, Kentaro Deguchi, Shoko Nagotani, Hanzhe Zhang, Xiquan Wang, Mikio Shoji, Mamoru Hasegawa, Koji Abe

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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 languageEnglish
Pages (from-to)731-739
Number of pages9
JournalNeurological Research
Volume30
Issue number7
DOIs
Publication statusPublished - 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

Jin, G., Inoue, M., Hayashi, T., Deguchi, K., Nagotani, S., Zhang, H., Wang, X., Shoji, M., Hasegawa, M., & Abe, K. (2008). Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury. Neurological Research, 30(7), 731-739. https://doi.org/10.1179/174313208X305418