Neuroprotective Effect of Ginkgo Biloba and its Bioactive Components Ischemia

银杏叶及其生物活性成分对缺血的神经保护作用

• 批准号: 7934996
• 负责人: Zahoor Ahmad Shah
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF TOLEDO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934996
• 关键词: Acute; Address; Affect; Aftercare; Age; Alzheimer' s Disease; Animal Model; Antioxidants; Anxiety; Autoradiography; Award; Behavioral; Behavioral Sciences; Bilirubin; Biliverdine; Biological; Biological Factors; Blood Vessels; Blood Viscosity; Blood flow; Brain; Brain Injuries; Carbon Monoxide; Cause of Death; Cell Death; Cell Survival; Cells; Cephalic; Cerebrovascular Circulation; Cerebrum; Cessation of life; China; Comparative Study; Confusion; Data; Disease; Dizziness; Dose; Environment; Erythrocytes; Flavonols; France; Future; Germany; Ginkgo biloba; Ginkgo biloba extract; Glucose; Glutamates; Glycosides; Goals; HOI; Headache; Heme; Herbal Medicine; Hippocampus (Brain); In Vitro; Individual; Infarction; Inflammation; Injury; Iron; Ischemia; Ischemic Brain Injury; Knock-out; Knowledge; Lactones; Laser-Doppler Flowmetry; Left; Materials Testing; Measures; Mediating; Memory; Mental Depression; Mentors; Methods; Middle Cerebral Artery Occlusion; Modeling; Molecular Biology; Mus; Nerve Degeneration; Neurodegenerative Disorders; Neuronal Dysfunction; Neurons; Neurosciences; Neurotransmitters; Outcome; Oxidative Stress; Oxygen; Oxygenases; Patients; Pharmaceutical Preparations; Physiological; Plant Extracts; Property; Proteomics; Protocols documentation; Publishing; Reactive Oxygen Species; Reperfusion Therapy; Reporting; Research; Research Personnel; Research Proposals; Resistance; Riots; Role; Stress; Stroke; Stroke prevention; System; Terpenes; Testing; Therapeutic; Time; Tinnitus; Toxic effect; Traditional Medicine; Training; Vascular blood supply; Work; bilobalide; career; clinically relevant; deprivation; experience; fight against; functional outcomes; ginkgolide A; ginkgolide B; heme oxygenase-1; improved; in vitro Model; in vivo; inhibitor/antagonist; innovation; inorganic phosphate; insight; knockout animal; medical schools; neuron loss; neuroprotection; neurosurgery; novel; post-doctoral training; pre-clinical; prevent; prophylactic; protective effect; skills

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.

我在神经外科方面的专业知识和技能，特别是在小动物模型方面，以及我在以下方面的知识： 草药和蛋白质组学对于中风和缺血性中风领域的研究进展至关重要， 脑损伤由于中风是美国第三大常见死因，因此该领域的研究 非常重要。我对这个临床相关的问题做出了一些贡献。比如我 最近发表了一种在小鼠中产生短暂性中风的优化方法， 还优化了永久性缺血模型。我已经使用这两种方法来测试有益的 其他标准化的草药植物提取物及其生物活性成分对中风的特性。我 长期目标包括研究天然产品，如银杏（EGb 761），以发现新的 预防和治疗中风和缺血相关脑损伤的机制。当我开始第五年的时候 在博士后培训中，我的近期目标是成为一名独立的前沿研究人员。 缺血相关神经元损伤的研究。除了我在中风和草药方面的经验外， 医学，这个建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 这是我实现独立职业目标所必需的我将与我的导师多尔博士合作， 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 并且有着良好的训练记录培训环境还包括一个顶级研究人员团队 在约翰霍普金斯医学院的行为神经科学，中风和衰老。K99/ROO奖 将使我有必要的时间和支持来实现我的研究目标。的主要目标 本研究拟探讨银杏叶提取物对缺血性脑损伤的神经保护作用及其作用机制。 使用永久性、短暂性和整体缺血模型进行脑损伤。我们已经积累了证据 血红素氧合酶1（HO 1）活性降低缺血性脑损伤，我们假设EGb提供 通过诱导HO 1的神经保护作用。为了确定HO 1在EGb神经保护中的作用，我们将 野生型小鼠和HO 1靶向缺失小鼠（HOT“）对缺血模型的影响并比较 EGb治疗前后对损伤大小的影响。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， HO 1表达和各种体外和体内缺血模型的功能结果。本研究 该提案将通过以下方式具有直接的临床前相关性：1）确定EGb在治疗或预防 中风相关损伤，2）确定EGb使用的最佳剂量和时间范围，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EGb的信息。