Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons.
To develop a novel strategy to prevent delayed neuronal death (DND) following transient occlusion of arteries, the gene of hepatocyte growth factor (HGF), a novel neurotrophic factor, was transfected into the subarachnoid space of gerbils after transient forebrain ischemia. Importantly, transfection of HGF gene into the subarachnoid space prevented DND, accompanied by a significant increase in HGF in the cerebrospinal fluid. Prevention of DND by HGF is due to the inhibition of apoptosis through the blockade of bax translocation from the cytoplasm to the nucleus. HGF gene transfer into the subarachnoid space may provide a new therapeutic strategy for cerebrovascular disease.
Hayashi
K
K
Department of Neurosurgery, Gifu University School of Medicine, Gifu, Japan.
Morishita
R
R
Nakagami
H
H
Yoshimura
S
S
Hara
A
A
Matsumoto
K
K
Nakamura
T
T
Ogihara
T
T
Kaneda
Y
Y
Sakai
N
N
D000818:Animals; D017209:Apoptosis; D015316:Genetic Therapy / Q000379:methods*; D005849:Gerbillinae; D017228:Hepatocyte Growth Factor / Q000134:cerebrospinal fluid / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D015552:Injections, Intralesional; D008297:Male; D009474:Neurons / Q000166:cytology; D018108:Respirovirus / Q000235:genetics; D020521:Stroke / Q000134:cerebrospinal fluid / Q000628:therapy*; D013346:Subarachnoid Space; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D014178:Translocation, Genetic; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D017228:Hepatocyte Growth Factor; D001616:beta-Galactosidase