Influence of EGF/bFGF treatment on proliferation, early neurogenesis and infarct volume after transient focal ischemia
Influence of EGF/bFGF treatment on proliferation, early neurogenesis and infarct volume after transient focal ischemia
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EGF/bFGF治疗对一过性局灶性缺血后增殖、早期神经发生和梗死体积的影响
DOI：
10.1016/j.brainres.2005.07.035
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发表时间：
2005-09-21
期刊：
影响因子：
2.9
通讯作者：
Reymann, KG
中科院分区：
文献类型：
--
作者：
Baldauf, K;Reymann, KG
成年哺乳动物前脑神经发生的持续性表明，内源性前体可能是损伤或神经变性后神经元替代的潜在来源。另一方面，碱性成纤维细胞生长因子（bFGF）和表皮生长因子（EGF）可以促进成年啮齿动物室下区（SVZ）和齿状回的神经前体增殖。由于EGF和bFGF的应用被发现可以促进全脑缺血后的神经发生，在这项研究中，我们研究了联合脑室内（i. c. v.）在成年雄性Sprague-Dawley大鼠短暂局灶性缺血的内皮素-1模型中，为期2周的EGF/bFGF治疗也影响新生成细胞的增殖。如甲苯胺蓝染色所评估的，FGF/bFGF显著增加缺血动物的梗死体积。慢性5 '-溴脱氧尿苷（BrdU）i. c. v.应用显示，手术后14天，侧脑室中FGF/bFGF诱导的细胞增殖增加。缺血后纹状体的增殖增加，而在齿状回和背侧第三脑室的细胞数量减少。通过与doublecortin（DCX）抗体共染色对这些细胞的神经元晚期的分析表明，生长因子伴随着缺血动物的同侧纹状体中的早期神经发生几乎加倍，但在齿状回中减少了早期神经发生。由于梗死体积增加和长期结果不明确，在对这种方法的前景做出最终结论之前，需要对慢性治疗方案进行进一步修改。(c)2005 Elsevier B. V.保留所有权利。
The persistence of neurogenesis in the adult mammalian forebrain suggests that endogenous precursors may be a potential source for neuronal replacement after injury or neurodegeneration. On the other hand basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) can facilitate neural precursor proliferation in the adult rodent subventricular zone (SVZ) and dentate gyrus. As the application of EGF and bFGF was found to boost neurogenesis after global ischemia, in this study we investigated whether a combined intracerebroventricular (i.c.v.) EGF/bFGF treatment over a period of 2 weeks affects the proliferation of newly generated cells in the endothelin-1 model of transient focal ischemia in adult male Sprague-Dawley rats as well. As assessed by toluidine blue staining, FGF/bFGF substantially increased the infarct volume in ischemic animals. Chronic 5'-bromodeoxyuridine (BrdU) i.c.v. application revealed an FGF/bFGF-induced increase in cell proliferation in the lateral ventricle 14 days after surgery. Proliferation in the striatum increased after ischemia, whereas in the dentate gyrus and in the dorsal 3rd ventricle the number of cells decreased. Analysis of the neuronal late of these cells by co-staining with a doublecortin (DCX) antibody showed that the growth factors concomitantly nearly doubled early neurogenesis in the ipsilateral striatum in ischemic animals but diminished it in the dentate gyrus. Because of the increased infarct volume and unclear long-term outcome further modifications of a chronic treatment schedule are needed before final conclusions concerning the perspectives of such an approach can be made. (c) 2005 Elsevier B.V. All rights reserved.