Neurogenesis after Stroke:Effect of Growth Factors

描述（由申请人提供）：本申请的长期目标是了解并最终改善成人大脑试图从短暂性局灶性缺血缺损中愈合的过程。中风仍然是成年人神经系统的主要破坏性残疾。我们目前的研究重点是预防中风，需要与强调中风后修复和恢复过程的研究相平衡。这项研究强调了一个新的发现，即成年人的大脑在海马体中发育神经祖细胞，即使是远程缺血性损伤也会刺激这些细胞。该项目强调刺激这些祖细胞增殖的因素。以后的研究将审查其生存，分化和迁移的控制。该提案的具体目标将强调短暂脑缺血后啮齿动物体内增殖模型。我们将使用齿状回细胞增殖的模型，并检查假设的生长因子的影响和机制，这些影响从梗死到远程网站的交付。第二个具体目标是通过体外培养来源于缺血性和非缺血性动物的祖细胞来分析这些细胞本身。该模型将测试它们对生长因子的敏感性。将通过微阵列分析和ELISA在缺血动物中进一步分析生长因子以增加生长因子的产生。从这些研究中获得的信息将使我们能够在缺血时增强这种细胞增殖的自然过程，并为刺激局灶性脑缺血后的神经可塑性奠定基础。

DESCRIPTION (provided by applicant): The long term objective of this application is to understand and eventually improve the process by which the adult brain attempts to heal from a transient focal ischemic deficit. Stroke remains the major devastating disabler for the adult neurologic system. Our present research focus on the prevention of stroke needs to be balanced with studies that emphasize the process of repair and recovery after stroke. This study highlights the new finding that the adult brain develops neuroprogenitor cells in the hippocampus, which are stimulated in response to even a remote ischemic injury. The project emphasizes those factors which stimulate the proliferation of these progenitor cells. Later studies will examine the control of their survival, differentiation and migration. The specific aims of this proposal will emphasize in vivo models of proliferation in the rodent after transient cerebral ischemia. We will use a model of dentate gyrus cell proliferation and examine hypothesized growth factor effects and the mechanism of delivery of those effects from the infarct to a remote site. The second specific aim will analyze these cells themselves by in vitro culturing of the progenitor cells derived from both ischemic and non-ischemic animals. This model will test their susceptibility to growth factors. Growth factors will be further analyzed by microarray analysis and ELISA in the ischemic animals for increased production of the growth factors. Information from these studies will allow us to enhance this natural process of cell proliferation at the time of ischemia and lay the groundwork for stimulation of neuroplasticity after focal cerebral ischemia.