Published Online
on May 1, 2003

A more recent version of this article appeared on June 1, 2003

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Submitted on December 11, 2002
Accepted on December 12, 2002

Adenovirus-Mediated Gene Transfer of Fibroblast Growth Factor-2 Increases BrdU-Positive Cells After Forebrain Ischemia in Gerbils

Norihiro Matsuoka MD; Kazuhiko Nozaki MD^*; Yasushi Takagi MD; Masaki Nishimura MD; Junya Hayashi MD; Shin-Ichi Miyatake MD; and Nobuo Hashimoto MD

Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto (N.M., K.N., Y.T., M.N., J.H., N.H.), and Department of Neurosurgery, Osaka Medical College, Takatsuki (S.-I.M.), Japan.

^* To whom correspondence should be addressed. E-mail: noz{at}kuhp.kyoto-u.ac.jp.

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.

Key words: adenovirus • bromodeoxyuridine • growth factors • ischemia • gerbils

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