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) onβ-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,andβ-catenin mRNA and protein expression,in neural stem cells were examined by immunohistochemistry,Western 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/reperfusion 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 ofβ-catenin andβ-catenin mRNA.In the ischemia/reperfusion group,the expression ofβ-catenin andβ-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,andβ-catenin mRNA had apparently increased in each group. CONCLUSION:bFGF promotes neural stem cell proliferation,and the expression ofβ-catenin andβ-catenin mRNA in the ischemic brain tissue.These findings indicate that bFGF promotion of neural stem cell proliferation may be mediated by Wnt/β-catenin signaling pathway. 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. 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. 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 ischemi a / 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. 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, . 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, Western blot, RT-PCR, and in situ hybridization techniques. the sham-operated group, only a few BrdU-immunoreactive neural stem cells were found.In the ischemia / reperfusion group, BrdU-immunoreactive cells began to increase from 3 days after ischemia / reperfusion induction, reached a peak level at 7 days, and gradually increased 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. showed slight expression of β-catenin and β-catenin mRNA. In the ischemia / reperfusion group, the expression of β-catenin and β-catenin mRNA gradually increased with reperfusion time, peaked at 14 days after reperfusion, and gradually subsequently thereafter; by 21 days, the expression was markedly lower.Following bFGF injection, the expression of hippocampal BrdU, β-catenin, andβ-catenin mRNA had apparently increased in each group. CONCLUSION: bFGF as neural stem cell proliferation, and the expression ofβ-ca tenin and β-catenin mRNA in the ischemic brain tissue. These findings of bFGF promotion of neural stem cell proliferation may be mediated by Wnt / β-catenin signaling pathway.