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BACKGROUND: The Wnt/β -catenin signaling pathway plays an important role in neural development. Β-catenin is an important component of the Wnt/β -catenin signaling pathway. The Wnt signaling pathway has been shown to regulate the interaction of neural stem cells with the extracellular matrix.OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) on β-catenin protein and mRNA expression, and on hippocampal neural stem cell proliferation in a rat model of cerebral ischemia/reperfusion.DESIGN, TIME AND SETTING: A randomized, controlled, neurobiology experiment was performed in Shenyang Medical College between August 2006 and August 2008.MATERIALS: A total of 72 healthy male Wistar rats, aged 3 months, were used in this study. bFGF was provided by Beijing SL Pharmaceutical Co.,Ltd., China.METHODS: Rats were randomly divided into 3 groups: sham-operated, ischemia/reperfusion, and bFGF-treated (n = 24 per group). Focal cerebral ischemia/reperfusion was induced in rats from the ischemia/reperfusion group and the bFGF-treated group by 2 hour right middle cerebral artery occlusion and 2 hour restoration of blood flow using the suture method. The ischemia/reperfusion and bFGF-treated groups were intraperitoneally administered 500 IU/mL of bFGF, or the same volume of physiological saline, once a day at postoperative days 1-3, and once every 3 days thereafter. Simultaneously, the sham-operated group underwent experimental procedures identical to the ischemia/reperfusion and bFGF-treated groups, with the exception of ischemia/reperfusion induction and drug administration. At 2 hours, 2, 6, 13, and 20 days after ischemia/reperfusion induction, 50 mg/kg bromodeoxyuridine (BrdU) was administered to each group, twice daily, to label proliferating neural stem cells.MAIN OUTCOME MEASURES: The effects of bFGF on BrdU labeling, and β-catenin mRNA and protein expression, in neural stem cells were examined by immunohistochemistry, West blot, RT-PCR, and in situ hybridization techniques.RESULTS: In the sham-operated group, only a few BrdU-immunoreactive neural stem cells were found. In the ischemia/repeffusion group, BrdU-immunoreactive cells began to increase from 3 days after ischemia/reperfusion induction, reached a peak level at 7 days, and gradually reduced from 21 days. At 3, 7, 14, and 21 days after ischemia/reperfusion induction, the numbers of BrdU-immunoreactive cells were significantly greater in the bFGF-treated group than in the ischemia/reperfusion group. The sham-operated group exhibited slight expression of β-catenin and β-catenin mRNA. In the ischia/reperfusion group, the expression of β-catenin and β-catenin mRNA gradually increased with reperfusion time, peaked at 14 days after reperfusion, and gradually decreased thereafter; by 21 days, the expression was markedly lower. Following bFGF injection, the expression of hippocampal BrdU, β -catenin, and β-catenin mRNA had apparently increased in each group.CONCLUSION: bFGF promotes neural stem cell proliferation, and the expression of β-catenin and β-catenin mRNA in the ischic brain tissue. These findings indicate that bFGF promotion of neural stem cell proliferation may be mediated by Wnt/β-catenin signaling pathway.