Role of soluble ST2 in immune cell regulation and secondary neurologic injury after intracerebral hemorrhage

可溶性ST2在脑出血后免疫细胞调节和继发性神经损伤中的作用

• 批准号: 10385742
• 负责人: Matthew Bradford Bevers
• 金额: $ 23.42万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10385742
• 关键词: Acute; Adaptor Signaling Protein; Address; Admission activity; Anti-Inflammatory Agents; Binding; Biological Response Modifiers; Brain Edema; Brain Injuries; Brain hemorrhage; Cell physiology; Cells; Cerebral Edema; Cerebral hemisphere hemorrhage; Clinical; Complex; Critical Care; Cytometry; Data Analyses; Deterioration; Development; Development Plans; Edema; Effector Cell; Enrollment; Environment; Equilibrium; Functional disorder; General Hospitals; Goals; Hematoma; Hemorrhage; Hospitals; Hour; Immune; Immunology; Inflammation; Inflammation Mediators; Inflammatory; Injury; Institution; Investigation; Laboratories; Lead; Link; Lobar; Location; Lymphocyte; Massachusetts; Measures; Mediating; Mediation; Mentors; Mentorship; Molecular Target; MyD88 protein; Natural Killer Cells; Nervous System Trauma; Neurologic; Neurological outcome; Neurologist; Neurology; Outcome; Pathway interactions; Patients; Pattern; Peripheral; Peripheral Blood Mononuclear Cell; Population; Prospective cohort; Proteins; Regulation; Regulatory T-Lymphocyte; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Scanning; Secondary to; Signal Transduction; Stroke; Structure; Survivors; System; T cell regulation; T-Lymphocyte; TLR4 gene; Tissues; Training; Universities; Water; Woman; X-Ray Computed Tomography; adaptive immune response; blood product; brain parenchyma; career; career development; cell injury; cerebrovascular; clinical predictors; cohort; cytokine; disability; effective therapy; experience; follow-up; functional outcomes; healthy volunteer; improved; insight; medical schools; monocyte; mortality; multidimensional data; neurological recovery; neurovascular injury; new therapeutic target; novel; novel therapeutics; patient oriented research; predictive marker; prevent; prospective; receptor; recruit; secondary analysis; skills; standard of care

Project Summary/Abstract Dr. Matthew B. Bevers is a neurologist in the divisions of Stroke, Cerebrovascular, and Critical Care Neurology at Brigham and Women's Hospital (BWH) whose goal is to become an independent investigator with expertise in mechanisms of secondary brain injury after intracerebral hemorrhage (ICH). His career development plan leverages the resources of a world-class training environment by bringing together a team of mentors and collaborators at a leading academic institution, Harvard Medical School, including both BWH and the Massachusetts General Hospital. Dr. Bevers has already obtained preliminary results supporting a role for the IL33/ST2 pathway in the pathophysiology of intracerebral hemorrhage and demonstrating the feasibility of his proposed studies into its role in the development of perihematomal edema and regulation of T cell and monocyte populations. Under the primary mentorship of Dr. W. Taylor Kimberly at MGH with a mentorship committee including Drs. Page Pennell and Francisco Quintana at BWH and scientific advisors including Drs. Lauren Sansing and Kevin Sheth at Yale University, Dr. Bevers proposes: 1) To identify a link between increases in a regulator of immune cell function – soluble ST2 – and perihematomal edema and functional outcome after ICH and 2) to identify changes in populations of immune effector cells associated with elevated sST2 and 3) to show the effect of manipulating the ST2/IL33 system on those immune cells. The overall goal of this project is to begin to explore a mechanistic pathway by which the initial injury from intracerebral hemorrhage leads to initiation of cerebral edema and ultimate neurologic outcome. By bringing together novel conceptual and technical approaches to the study of brain edema and immunology, this project will generate new insights into mechanisms of secondary brain injury. In the long term, Dr. Bevers' career goal is to identify unique molecular targets and develop novel therapies to improve neurologic recovery after hemorrhagic stroke. The proposed patient-oriented research project, along with mentorship and structured career development and scientific training, will provide Dr. Bevers with the skills and experience needed to become an independent investigator in the field of acute neurovascular injury.

项目摘要/摘要 Matthew B. Bevers博士是中风，脑血管和重症监护神经病学的神经科医生 在Brigham and妇女医院（BWH）的目标是成为具有专业知识的独立调查员 脑出血（ICH）后继发性脑损伤的机制。他的职业发展计划 通过汇集一组导师和 哈佛大学领先的学术机构的合作者，包括BWH和 马萨诸塞州综合医院。 Bevers博士已经获得了支持该角色的初步结果 脑出血的病理生理学中的IL33/ST2途径，并证明了他的可行性 拟议的研究涉及其在围围围肿瘤的发展以及T细胞和调节的作用中的作用 单核细胞种群。在MGH的W. Taylor Kimberly博士的主要心态下 委员会包括博士。 Page Pennell和BWH的Francisco Quintana以及包括Drs在内的科学顾问。 耶鲁大学的Lauren Sansing和Kevin Sheth，Bevers Dr.建议：1）确定 免疫细胞功能调节剂的增加 - 固体ST2 - 和近日血肿水肿和功能 ICH之后的结果和2）确定与升高有关的免疫效应细胞种群的变化 SST2和3）显示操纵ST2/IL33系统对这些免疫细胞的影响。总体目标 该项目的开始探索一种机械途径，脑内最初受伤 出血会导致脑水肿和最终神经系统结局的启动。通过汇集小说 研究大脑水肿和免疫学研究的概念和技术方法，该项目将产生 对继发性脑损伤机制的新​​见解。从长远来看，Bevers博士的职业目标是确定 独特的分子靶标并开发出新的疗法，以改善出血性中风后神经系统恢复。 拟议的面向患者的研究项目，指导和结构化的职业发展以及 科学培训将为Bevers博士提供成为独立的技能和经验 急性神经血管损伤领域的研究者。