Neuroprotective Effect of Ginkgo Biloba and its Bioactive Components Ischemia

我在神经外科，特别是在小动物模型方面的专业知识和技能，以及我对 草药和蛋白质组学对促进卒中和脑缺血领域的研究至关重要 脑部受损。由于中风是美国第三大常见死亡原因，这一领域的研究 非常重要。我为这个临床相关的问题做出了许多贡献。例如，我 最近发布了一种在小鼠中产生短暂性中风的优化方法，并已被 还优化了一个永久性的缺血模型。我使用了这两种方法来测试有益的 其他标准化的草本植物提取物及其抗中风生物活性成分的特性。我的 长期目标包括研究天然产品，如银杏(Ginkgo Biloba)(EGb 761)，以发现新的 预防和治疗中风和缺血性脑损伤的机制。当我开始五年级的时候 在博士后培训方面，我的近期目标是成为一名独立的尖端研究员 脑缺血相关神经元损伤的研究进展。除了我在中风和草药方面的经验 医学，这个提议将使我能够完成我在行为科学和分子生物学方面的培训 这是实现我独立的职业目标所必需的。我将与我的导师多尔博士一起工作，他已经 在与中风和其他神经退行性疾病相关的神经元功能障碍方面拥有丰富的专业知识 并有训练员的良好记录。培训环境还包括一支顶尖研究人员团队 约翰霍普金斯医学院的行为神经科学、中风和衰老。K99/Roo奖 这将使我有时间和必要的支持来实现我的研究目标。该计划的主要目标是 本研究旨在探讨银杏叶提取物对脑缺血的神经保护作用及其机制。 使用永久性、暂时性和全局性脑缺血模型造成的脑损伤。我们已经积累了证据 血红素加氧酶1(HO1)的活性减少了缺血性脑损伤，我们假设EGB提供了 通过诱导HO1进行神经保护。为了确定HO1在EGb神经保护中的作用，我们将 野生型和靶向缺失HO1(HOT‘“)小鼠对缺血模型的影响及效果比较 治疗前后银杏叶提取物对损伤大小的影响。我们还将优化治疗剂量和窗口。我们 将通过测量脑血流量、海马细胞死亡、 在不同的体外和体内缺血模型中HO1的表达和功能结果。这项研究 通过1)确定银杏叶提取物在治疗或预防方面的疗效，建议将具有直接的临床前相关性 与中风相关的伤害，2)确定使用银杏叶提取物的最佳剂量和时间框架，以及3)提供 为临床医生和他们的患者提供关于预防性使用银杏提取物的信息。

My expertise and skill in neurosurgery, particularly in small animal models, together with my knowledge of herbal drugs and proteomics are essential to the advancement of research in the field of stroke and ischemic brain damage. Because stroke is the third most common cause of death in the US, research in this field is of great importance. I have made a number of contributions to this clinically relevant problem. For example, I have recently published an optimized method for producing transient stroke in mice, and have been optimizing a permanent model of ischemia also. I have used both of these methods to test the beneficial properties of other well standardized herbal plant extracts and their bioactive components against stroke. My long term goals involve researching natural products, such as Ginkgo biloba (EGb 761), to find novel mechanisms for preventing and treating stroke and ischemia-related brain injury. While starting my fifth year of postdoctoral training, my immediate goal is to become an independent researcher in the cutting-edge research of neuronal damage associated with ischemia. In addition to my experience in stroke and herbal medicine, this proposal will allow me to complete my training in behavioral science and molecular biology which is necessary to reach my independent career goals. I will work with my mentor, Dr. Dore, who has extensive expertise in neuronal dysfunction associated with stroke and other neurodegenerative diseases and has a proven record of training fellows. The training environment also involves a team of top researchers in behavioral neuroscience, stroke, and aging at the Johns Hopkins School of Medicine. The K99/ROO award will allow me the time and support necessary to work toward my research goals. The main goal of the proposed project is to determine the neuroprotective effect and mechanism of actions of EGb in ischemic brain injury by using permanent, transient, and global models of ischemia. We have accumulated evidence that heme oxygenase 1 (HO1) activity reduces ischemic brain injury, and we hypothesize that EGb provides neuroprotection by inducing HO1. To determine the role of HO1 in EGb neuroprotection, we will subject wildtype mice and mice with targeted deletion of HO1 (HOT'") to models of ischemia and compare the effect of EGb pre- and post-treatment on injury size. We will also optimize the therapeutic dose and window. We will address possible mechanisms of protection by measuring cerebral blood flow, hippocampal cell death, HO1 expression, and functional outcomes in various in vitro and in vivo ischemia models. This research proposal will have direct pre-clinical relevance by 1) determining the efficacy of EGb in treating or preventing stroke-related injury, 2) determining the optimal dose and time frame for EGb use, and 3) providing information for clinicians and their patients regarding the prophylactic use of Ginkgo extract, EGb.