Metabolomic analysis of acute stress hyperglycemia in ischemic stroke

缺血性脑卒中急性应激性高血糖的代谢组学分析

• 批准号: 8224628
• 负责人: William Taylor Kimberly
• 金额: $ 17.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8224628
• 关键词: Address; Adult; Blood Glucose; Boston; Brain; Branched-Chain Amino Acids; Caring; Cause of Death; Cerebrovascular Disorders; Clinical; Development; Development Plans; Diabetes Mellitus; Disease; Educational Curriculum; Environment; Fatigue; General Hospitals; Glucose; Goals; Human; Hyperglycemia; Institution; Insulin Resistance; Investigation; Ischemia; Ischemic Stroke; Isoleucine; Knowledge; Leucine; Mass Spectrum Analysis; Massachusetts; Mentors; Mentorship; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolism; Methods; Nervous System Trauma; Neurological outcome; Neurologist; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Outcome; Patients; Physiological; Play; Prevention; Process; Research; Research Personnel; Research Proposals; Resources; Rodent Model; Role; Science; Stroke; Structure; Surveys; Technology; Time; Transient Ischemic Attack; United States; Valine; acute stress; acute stroke; base; bench to bedside; career; career development; cerebrovascular; disability; glucose metabolism; impaired glucose tolerance; indexing; innovation; metabolic abnormality assessment; metabolomics; novel; novel strategies; patient oriented research; programs; response; skills; treatment strategy

DESCRIPTION (provided by applicant): Dr. W. Taylor Kimberly is a Neurocritical Care and Stroke Neurologist at Massachusetts General Hospital (MGH), whose goal is to become an independent investigator with expertise in metabolomics, insulin resistance and to define its contribution to stroke and other cerebrovascular diseases. His career development plan leverages the resources of a world-class environment by bringing together an outstanding team of investigators centered at a leading academic institution in Boston, Massachusetts General Hospital. Dr. Kimberly has already obtained preliminary results demonstrating the feasibility of research plan that uses a novel metabolomic platform that can analyze more than 300 key metabolites at the same time. Under the mentorship of Dr. Robert Gerszten, and co-Mentors Dr. Greg Sorensen and Dr. Jose Florez, Dr. Kimberly proposes: 1) To determine whether branched chain amino acids are altered in the setting of stroke, 2) To determine whether hyperglycemia of stroke influences the way branched chain amino acids (valine, isoleucine and leucine) are altered, and 3) To prospectively investigate whether glucose metabolism and branched chain amino acid alterations will predict neurological outcomes. The overall goal is to elucidate the mechanisms that underlie hyperglycemia in acute stroke and to determine how this leads to worse neurological outcomes. Bringing together cutting-edge technology and a team with relevant expertise, this project will open new avenues for treatment in stroke. This well-defined patient-oriented research proposal, in concert with mentorship and a structured didactic curriculum, will provide Dr. Kimberly with the skills that are essential for him to develop an independent career in cerebrovascular research at the cutting edge of science. PUBLIC HEALTH RELEVANCE: Despite modern advances in prevention and treatment, stroke remains the leading cause of adult disability and the second leading cause of death worldwide. Dr. Kimberly's proposed career development plan has outstanding potential to advance our knowledge of the interaction between metabolism and ischemic stroke, which is a crucial step towards the discovery of novel treatment strategies.

描述（由申请人提供）：W. Taylor Kimberly是马萨诸塞州总医院（MGH）的神经重症监护和中风神经学家，其目标是成为一名独立的研究者，在代谢组学，胰岛素抵抗方面具有专业知识，并确定其对中风和其他脑血管疾病的贡献。他的职业发展计划利用世界一流环境的资源，汇集了一支以波士顿领先学术机构马萨诸塞州总医院为中心的优秀研究团队。Kimberly博士已经获得了初步结果，证明了研究计划的可行性，该计划使用了一种新的代谢组学平台，可以同时分析300多种关键代谢物。在Robert Gerszten博士以及共同导师Greg Sorensen博士和Jose Florez博士的指导下，Kimberly博士提出：1）确定支链氨基酸是否在中风的情况下改变，2）确定中风的高血糖是否影响支链氨基酸的方式，（缬氨酸、异亮氨酸和亮氨酸）改变，和3）前瞻性研究葡萄糖代谢和支链氨基酸改变是否将预测神经学结果。总体目标是阐明急性卒中高血糖的机制，并确定高血糖如何导致更差的神经功能结局。该项目汇集了尖端技术和具有相关专业知识的团队，将为中风治疗开辟新的途径。这个明确的以患者为导向的研究计划，与导师制和结构化的教学课程相结合，将为金伯利博士提供在科学前沿发展脑血管研究独立职业所必需的技能。 公共卫生关系：尽管在预防和治疗方面取得了现代进步，但中风仍然是全球成人残疾的主要原因和第二大死亡原因。金伯利博士提出的职业发展计划具有突出的潜力，可以促进我们对代谢和缺血性中风之间相互作用的认识，这是发现新治疗策略的关键一步。