Epidermal growth factor-induced cell proliferation in the adult rat striatum.
Epidermal growth factor-induced cell proliferation in the adult rat striatum.
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表皮生长因子诱导成年大鼠纹状体细胞增殖。
DOI：
10.1016/j.brainres.2003.12.054
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Colello,RaymondJ
中科院分区：
文献类型：
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作者：
McGinn,MelissaJ;Sun,Dong;Schneider,StacieL;Alexander,JohnK;Colello,RaymondJ
目前修复成人中枢神经系统损伤的策略包括细胞移植和/或使用病毒载体输送治疗剂。尽管这两种技术前景看好，但由于外来抗原的引入在大脑中引发了免疫反应，这两种技术的实用性都受到了限制。修复受损中枢神经系统的另一种方法是刺激大脑内的内源性细胞分裂，从而取代因损伤而失去的细胞。由于已经证明生长因子如表皮生长因子(EGF)在体外对CNS细胞是强有力的有丝分裂原，我们试图评估EGF在成年哺乳动物脑中的体内促有丝分裂作用。相应地，将不同剂量的重组人表皮生长因子注射到成年大鼠的纹状体内，48h后，腹腔注射5-溴脱氧尿苷(BrdU)，这是细胞增殖的标志。在评估的四种剂量中，0.05毫微克的EGF诱导的细胞增殖水平最高。为了确定这些增殖细胞的细胞特性，动物在给予EGF后48h注射~3H-胸腺嘧啶核苷标记分裂细胞。切片随后进行星形胶质细胞、小胶质细胞、少突胶质细胞、神经前体细胞和成熟神经元的标记免疫组织化学染色。与对照组相比，给予EGF的新生细胞中有相当大一部分被鉴定为未成熟和成熟的星形胶质细胞。总而言之，这些结果为利用生长因子给药方法动员内源性细胞的增殖反应以取代因损伤或疾病而失去的细胞提供了有价值的信息。
Current strategies for repairing the adult CNS following injury include cell transplantation and/or the use of viral vectors to deliver therapeutic agents. Although promising, both techniques are limited in their usefulness due to the immunological response triggered in the brain as a result of the introduction of foreign antigens. An alternative method to repair the damaged CNS is to stimulate endogenous cells within the brain to divide thereby replacing cells lost to injury. Since it has been shown that growth factors such as epidermal growth factor (EGF) are potent mitogens to CNS cells in vitro, we sought to assess the mitogenic effect of an in vivo application of EGF to the adult mammalian brain. Accordingly, varying doses of human recombinant EGF were administered to the striatum of adult rats, followed 48 h later by intraperitoneal injections of 5-bromodeoxyuridine (BrdU), a marker for cell proliferation. Of four doses assessed, 0.05 ng of EGF induced the highest levels of cell proliferation. To determine the cellular identity of these proliferating cells, animals were injected with3H-thymidine 48 h following EGF administration to label dividing cells. Sections were subsequently immunostained for markers to astrocytes, microglia, oligodendrocytes, neural precursors, and mature neurons. Compared to controls, a significant proportion of the newly generated cells resulting from EGF administration were identified as immature and mature astrocytes. Collectively, these results provide valuable information for utilizing a growth factor administration approach to mobilize the proliferative response of endogenous cells to replace those lost to injury or disease.