Postischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats.
Fibroblast growth factor (FGF)-2 is a potent neurotrophic and angiogenic peptide. To examine possible protective effects of FGF-2 gene expression against transient focal cerebral ischemia in rats, a replication defective, recombinant adenovirus vector expressing FGF-2, was injected intraventricularly 2 hours after middle cerebral artery occlusion (MCAO). The treatment group showed significant recovery compared with the vehicle-treated groups in terms of serial neurologic severity scores over the 35 days after MCAO. Further, 2,3,5-triphenyltetrazolium chloride staining showed that FGF-2 gene transfer decreased infarct volume by 44% as compared with that in the vehicle-treated groups at 2 days after MCAO. The same tendency of gene transfer effects on infarct volume was confirmed at 35 days after MCAO with hematoxylin/eosin staining. Enzyme-linked immunosorbent assay revealed that FGF-2 concentration was increased significantly at 2 days after MCAO, not only in cerebrospinal fluid but also in cerebral substance in the lesioned and treated animals. These results suggested that FGF-2 gene transfer using these adenoviral vectors might be a useful modality for the treatment of occlusive cerebrovascular disease even after the onset of stroke.
Watanabe
Takuji
T
Department of Neurosurgery, Osaka Medical College, Takatsuki 569-8686, Japan.
Okuda
Yasuaki
Y
Nonoguchi
Naosuke
N
Zhao
Ming Zhu
MZ
Kajimoto
Yoshinaga
Y
Furutama
Daisuke
D
Yukawa
Hiroyuki
H
Shibata
Masa-Aki
MA
Otsuki
Yoshinori
Y
Kuroiwa
Toshihiko
T
Miyatake
Shin-Ichi
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D020520:Brain Infarction / Q000150:complications* / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002545:Brain Ischemia / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D016896:Treatment Outcome
D016222:Fibroblast Growth Factor 2