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 马修·B·贝弗斯博士是中风、脑血管和重症监护神经科的神经科专家 在布里格姆妇女医院(BWH)，目标是成为一名具有专业知识的独立调查员 脑出血后继发性脑损伤机制的研究。他的职业发展计划 通过汇聚一组导师和 领先学术机构哈佛医学院的合作者，包括BWH和 麻省总医院。贝弗斯博士已经获得了初步结果，支持 IL33/ST2通路在脑出血病理生理中的作用及His的可行性 建议研究其在血肿周围水肿的发生发展中的作用以及对T细胞和 单核细胞群体。在MGH W.Taylor Kimberly博士的主要指导下，并在指导下 该委员会包括BWH的佩奇·彭内尔博士和弗朗西斯科·昆塔纳博士，以及包括帕奇·彭内尔和弗朗西斯科·昆塔纳博士在内的科学顾问。 耶鲁大学的劳伦·桑辛和凯文·谢斯博士建议：1)找出 免疫细胞功能调节因子--可溶性ST2的增加和血肿周围的水肿和功能性 脑出血后的结果和2)确定与升高相关的免疫效应细胞群的变化 Sst2和3)以显示操纵ST2/IL33系统对这些免疫细胞的影响。总目标 这个项目的目的是开始探索一种机制途径，通过它从脑内最初的损伤 出血会导致脑水肿和最终的神经学后果。通过将小说汇集在一起 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，贝弗斯博士的职业目标是确定 独特的分子靶点和开发新的治疗方法，以改善出血性中风后的神经恢复。 拟议的以患者为导向的研究项目，以及导师和结构化的职业发展和 科学培训，将为贝弗斯博士提供成为独立医生所需的技能和经验 急性神经血管损伤领域的研究人员。