Sendai virus vector-mediated gene transfer of glial cell line-derived neurotrophic factor prevents delayed neuronal death after transient global ischemia in gerbils.
We have developed a cytoplasmic replicating virus vector of Sendai virus (SeV) that infects and replicates in most mammalian cells, including neurons, and directs high-level gene expression. To investigate the protective effect of SeV vector-mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) on the delayed neuronal death caused by transient global ischemia in gerbils, SeV vectors carrying either GDNF (SeV/GDNF) or enhanced green fluorescent protein gene (SeV/GFP) were stereotaxically microinjected into the lateral ventricle. Four days after injection, occlusion of the bilateral common carotid arteries for 5 min produced transient global forebrain ischemia. Treatment with SeV/GDNF significantly decreased the delayed neuronal death of the hippocampal CA1 pyramidal neurons observed 6 days after the operation. TUNEL staining demonstrated that SeV/GDNF treatment markedly reduced the number of apoptotic cells in the hippocampal CA1 neurons, indicating that SeV/GDNF treatment prevented apoptosis. Furthermore, delayed neuronal death on the contralateral side of the hippocampal CA1 was also prevented to a similar extent as that on the ipsilateral side. These results suggest that SeV/GDNF prevents the delayed neuronal death induced by ischemia and is potentially useful for gene therapy for stroke.
Shirakura
Masayuki
M
DNAVEC Research Inc., 1-25-11 Kannondai, Tsukuba-shi, Ibaraki 305-0856, Japan.
Fukumura
Masayuki
M
Inoue
Makoto
M
Fujikawa
Satoshi
S
Maeda
Mitsuyo
M
Watabe
Kazuhiko
K
Kyuwa
Shigeru
S
Yoshikawa
Yasuhiro
Y
Hasegawa
Mamoru
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D017931:DNA Primers; D018014:Gene Transfer Techniques; D005849:Gerbillinae; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D009474:Neurons / Q000473:pathology*; D029082:Sendai virus / Q000235:genetics*
D017931:DNA Primers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors