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: 8326593
• 负责人: William Taylor Kimberly
• 金额: $ 19.46万
• 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/8326593
• 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; 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; didactic education; 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.

描述（由申请人提供）：W. Taylor Kimberly 博士是马萨诸塞州总医院 (MGH) 的神经重症监护和中风神经科医生，其目标是成为一名在代谢组学、胰岛素抵抗方面拥有专业知识的独立研究者，并确定其对中风和其他脑血管疾病的影响。他的职业发展计划利用了世界一流环境的资源，汇集了以波士顿领先学术机构马萨诸塞州综合医院为中心的优秀研究团队。 Kimberly博士已经获得了初步结果，证明了使用新型代谢组学平台的研究计划的可行性，该平台可以同时分析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) 确定支链氨基酸在中风的情况下是否发生改变，2) 确定中风的高血糖是否影响支链氨基酸（缬氨酸、异亮氨酸和亮氨酸）的改变方式，以及 3) 前瞻性研究葡萄糖是否会改变 代谢和支链氨基酸的改变将预测神经系统的结果。总体目标是阐明急性中风高血糖的机制，并确定其如何导致更糟糕的神经系统结果。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途径。这项明确的以患者为导向的研究计划，与指导和结构化的教学课程相结合，将为金伯利博士提供他在科学前沿的脑血管研究中发展独立职业所必需的技能。