Adenovirus-mediated gene transfer of fibroblast growth factor-2 increases BrdU-positive cells after forebrain ischemia in gerbils.
OBJECTIVE
Progenitor cells continue to generate neurons in the adult mammalian brain, and cerebral ischemia induces neurogenesis. We examined the efficacy of the intraventricular injection of a recombinant adenovirus-expressing fibroblast growth factor-2 (FGF-2) (AxCAMAssbFGF) on neurogenesis in both normal and ischemic brains.


METHODS
We used a gerbil model of transient global ischemia and counted the number of BrdU-positive cells after injection of AxCAMAssbFGF into the brain with or without ischemia.


RESULTS
Intraventricular AxCAMAssbFGF produced robust FGF-2 protein increases in diverse regions of the brain and markedly increased FGF-2 concentrations in cerebrospinal fluid 2 days after administration and evoked significant proliferation of BrdU-positive cells not only in the subventricular zone and dentate gyrus of the hippocampus but also in the cerebral cortex, and some BrdU-positive cells differentiated into neurons. Continuous intraventricular infusion of FGF-2 protein increased FGF-2 concentration in cerebrospinal fluid but not in brain tissues and produced BrdU-positive cell proliferation only in the subventricular zone of the lateral ventricle.


CONCLUSIONS
Adenovirally mediated transfer of the FGF-2 gene promoted progenitor cell proliferation more efficiently in widespread regions of the brain after transient global ischemia than continuous intraventricular infusion of FGF-2 protein.
Matsuoka
Norihiro
N
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Nozaki
Kazuhiko
K
Takagi
Yasushi
Y
Nishimura
Masaki
M
Hayashi
Junya
J
Miyatake
Shin-Ichi
S
Hashimoto
Nobuo
N
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D005849:Gerbillinae; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000628:therapy*; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology; D008297:Male; D016548:Prosencephalon / Q000098:blood supply / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology
D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine