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: 8223212
• 负责人: Zahoor Ahmad Shah
• 金额: $ 24.22万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 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 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8223212
• 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; 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); In Vitro; Individual; Infarction; Inflammation; Injury; Iron; Ischemia; Ischemic Brain Injury; Knock-out; Knowledge; Lactones; Laser-Doppler Flowmetry; 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，以及我的了解 草药和蛋白质组学对于中风和缺血领域的研究发展至关重要 脑损伤。由于中风是美国第三大常见的死亡原因，因此该领域的研究是 非常重视。我为这个临床上相关的问题做出了许多贡献。例如，我 最近发表了一种在小鼠中产生瞬态中风的优化方法，并且 还优化了缺血的永久模型。我已经使用了这两种方法来测试有益的 其他良好标准化的草药提取物及其对中风的生物活性成分的特性。我的 长期目标涉及研究天然产品，例如Ginkgo Biloba（EGB 761） 预防和治疗中风和缺血相关脑损伤的机制。开始我的第五年 在博士后培训中，我的近期目标是成为尖端的独立研究人员 与缺血有关的神经元损害的研究。除了我在中风和草药方面的经验 医学，该建议将使我能够完成行为科学和分子生物学的培训 达到我独立的职业目标是必要的。我将与我的导师Dr. Dore一起工作， 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的广泛专业知识 并拥有培训研究员的良好记录。培训环境还涉及一组顶级研究人员 约翰·霍普金斯医学院的行为神经科学，中风和衰老。 K99/ROO奖 将使我的时间和支持为实现我的研究目标所需的时间和支持。主要目标 拟议的项目是确定EGB在缺血性的神经保护作用和作用机理 通过使用永久性，瞬态和全球缺血模型，脑损伤。我们积累了证据 血红素氧酶1（HO1）活性减少了缺血性脑损伤，我们假设EGB提供 神经保护通过诱导HO1。为了确定HO1在EGB神经保护中的作用，我们将进行 Wildtype小鼠和靶向缺失HO1（热'）的小鼠对缺血模型并比较效果 EGB治疗前后有关伤害大小的治疗。我们还将优化治疗剂量和窗口。我们 将通过测量脑血流，海马细胞死亡，以解决保护的可能机制 HO1表达以及各种体外和体内缺血模型中的功能结果。这项研究 提案将通过1）确定EGB在治疗或预防的效力中具有直接的临床前相关性 中风相关的损伤，2）确定EGB使用的最佳剂量和时间范围，3）提供 临床医生及其患者有关银杏提取物的预防性使用EGB的信息。

项目成果

HO1 and Wnt expression is independently regulated in female mice brains following permanent ischemic brain injury.

• DOI: 10.1016/j.brainres.2017.02.006
• 发表时间: 2017-05-01
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Tulsulkar J;Ward A;Shah ZA
• 通讯作者: Shah ZA

Cofilin Inhibition Restores Neuronal Cell Death in Oxygen-Glucose Deprivation Model of Ischemia.

• DOI: 10.1007/s12035-014-9056-3
• 发表时间: 2016-03
• 期刊: MOLECULAR NEUROBIOLOGY
• 影响因子: 5.1
• 作者: Madineni, Anusha;Alhadidi, Qasim;Shah, Zahoor A.
• 通讯作者: Shah, Zahoor A.

Cofilin Mediates LPS-Induced Microglial Cell Activation and Associated Neurotoxicity Through Activation of NF-κB and JAK-STAT Pathway.

• DOI: 10.1007/s12035-017-0432-7
• 发表时间: 2018-03
• 期刊: Molecular neurobiology
• 影响因子: 5.1
• 作者: Alhadidi Q;Shah ZA
• 通讯作者: Shah ZA

Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2.

• DOI: 10.1016/j.nbd.2012.01.006
• 发表时间: 2012-04
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Nada, Shadia E.;Shah, Zahoor A.
• 通讯作者: Shah, Zahoor A.

Attenuation of stress-elicited brain catecholamines, serotonin and plasma corticosterone levels by calcined gold preparations used in Indian system of medicine.

印度医学体系中使用的锻金制剂可降低应激引起的脑儿茶酚胺、血清素和血浆皮质酮水平。

• DOI: 10.1111/j.1742-7843.2005.pto_10.x
• 发表时间: 2005
• 期刊: Basic & clinical pharmacology & toxicology
• 影响因子: 3.1
• 作者: Shah,ZahoorAhmad;Gilani,RabiaAfzal;Sharma,Pragya;Vohora,ShashiBharat
• 通讯作者: Vohora,ShashiBharat