Adenovirus-Mediated Gene Transfer of Fibroblast Growth Factor-2 Increases BrdU-Positive Cells After Forebrain Ischemia in Gerbils
作者:
Norihiro Matsuoka,
Kazuhiko Nozaki,
Yasushi Takagi,
Masaki Nishimura,
Junya Hayashi,
Shin-Ichi Miyatake,
Nobuo Hashimoto,
期刊:
Stroke: Journal of the American Heart Association
(OVID Available online 2003)
卷期:
Volume 34,
issue 6
页码: 1519-1525
ISSN:0039-2499
年代: 2003
出版商: OVID
关键词: adenovirus;bromodeoxyuridine;growth factors;ischemia;gerbils
数据来源: OVID
摘要:
Background and Purpose—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.
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