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: 7545532
• 负责人: Zahoor Ahmad Shah
• 金额: $ 8.95万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545532
• 关键词: Acute; Address; Affect; Aftercare; Aging; 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; Corpus striatum structure; Data; Disease; Dizziness; Dose; Environment; Erythrocytes; Flavonols; France; Future; Germany; Ginkgo biloba; Ginkgo biloba extract; Glucose; Glutamates; Glycosides; Goals; HOI; Headache; Health; Heme; Herbal Medicine; Hippocampus (Brain); Homeostasis; In Vitro; Individual; Infarction; Inflammation; Injury; Iron; Ischemia; Ischemic Brain Injury; Knock-out; Knowledge; Lactones; Laser-Doppler Flowmetry; Left; Materials Testing; Measures; Mediating; Memory; Mentors; Methods; Middle Cerebral Artery Occlusion; Modeling; Molecular; Molecular Biology; Mus; Nerve Degeneration; Neurodegenerative Disorders; Neuronal Dysfunction; Neurons; Neurosciences; Neurotransmitters; Outcome; Oxidative Stress; Oxygen; Oxygenases; Pathway interactions; Patients; Pharmaceutical Preparations; Physiological; Plant Extracts; Predisposition; Property; Proteomics; Protocols documentation; Publishing; Reactive Oxygen Species; Reperfusion Therapy; Reporting; Research; Research Personnel; Research Proposals; Resistance; Role; Stress; Stroke; Stroke prevention; System; Terpenes; Testing; Therapeutic; Time; Tinnitus; Toxic effect; Traditional Medicine; Training; Vascular blood supply; Work; bilobalide; career; clinically relevant; density; depression; deprivation; experience; fight against; free radical oxygen; 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; programs; prophylactic; protective effect; research study; skills; tool

DESCRIPTION (provided by applicant): 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/R00 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.

描述（由申请人提供）：我在神经外科手术方面的专业知识和技巧，尤其是在小动物模型中，以及我对草药药物和蛋白质组学的了解，对于中风和缺血性脑损伤的研究的发展至关重要。由于中风是美国第三大常见的死亡原因，因此该领域的研究非常重要。我为这个临床上相关的问题做出了许多贡献。例如，我最近发表了一种优化的方法，用于在小鼠中产生瞬态中风，并正在优化一种永久性缺血模型。我已经使用了这两种方法来测试其他良好标准化草药提取物的有益特性及其对中风的生物活性成分。我的长期目标涉及研究天然产物，例如银杏（EGB 761），以找到预防和治疗中风和缺血相关脑损伤的新型机制。在开始我的博士后培训的第五年时，我的近期目标是成为与缺血相关的神经元损害的尖端研究的独立研究人员。除了我在中风和草药方面的经验外，该建议还可以使我能够完成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Drore一起工作，他在与中风和其他神经退行性疾病有关的神经元功能障碍方面拥有广泛的专业知识，并且具有培训研究员的可靠记录。培训环境还涉及约翰·霍普金斯医学院的行为神经科学，中风和衰老的顶级研究人员。 K99/R00奖将使我为实现研究目标所需的时间和支持。拟议项目的主要目标是通过使用永久性，瞬态和全球缺血模型来确定EGB在缺血性脑损伤中的神经保护作用和机理。我们积累了证据表明血红素氧酶1（HO1）活性减少了缺血性脑损伤，我们假设EGB通过诱导HO1提供神经保护作用。 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各种体外和体内缺血模型的功能结果将通过1）确定EGB治疗或预防中风相关的损伤的疗效，2）确定EGB的最佳剂量和时间范围