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Quantitative proteomic analysis of the aging brain after intracerebral hemorrhage

脑出血后衰老大脑的定量蛋白质组学分析

基本信息

批准号：
10433541
负责人：
Sangeetha Sukumari-Ramesh
金额：
$ 7.7万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10433541
关键词：
Acute Address Age Aging Animal Model Animals Antibodies Anticoagulants Bioinformatics Brain Brain Injuries Cell Separation Cells Cerebral hemisphere hemorrhage Chronic Phase Complex Data Development Disease Elderly Flow Cytometry Functional disorder Genetic Goals Grant Hospitals Human In Vitro Incidence Inflammation Mediators Inflammatory Innate Immune System Investigation Ipsilateral Knowledge Label Laboratories Liquid Chromatography Mass Spectrum Analysis Mediating Microglia Mission Molecular Mus National Institute of Neurological Disorders and Stroke Neurological outcome Pathology Pathway interactions Patient-Focused Outcomes Patients Phagocytes Phagocytosis Pharmacology Play Pre-Clinical Model Prevalence Process Prognosis Proteins Proteome Proteomics Public Health Reporting Research Research Personnel Role Stroke Therapeutic Intervention Time Translations adverse outcome aged aging brain base brain repair cell type clinically relevant disability effective therapy experience improved in vivo injury and repair macrophage molecular targeted therapies monocyte mortality novel novel therapeutic intervention patient population pre-clinical preclinical study response tandem mass spectrometry tool

项目摘要

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with no effective treatment. Lack of treatment options partly contributes to the poorly defined pathophysiology of ICH. Along these lines, despite the increasing prevalence of ICH in the elderly, the molecular level changes that occur in the aging brain after ICH remains largely enigmatic. To address this critical knowledge gap, two specific aims are proposed. Aim 1: To determine the age-induced changes in the brain proteome after ICH. Aim 2: To determine the age-induced protein level changes in microglia and brain-infiltrating monocyte-derived macrophages (BMDM) after ICH. The proposed studies employ a preclinical model of ICH and include unbiased and rigorous proteomics approaches such as label-free and TMT-labeling Mass spectrometry and bioinformatics approaches. Successful completion of the project would identify novel molecular regulators to improve the neurological outcomes after ICH in the elderly. Also, the studies would define, for the first time, the proteomic profile of acutely isolated microglia and macrophages, the cells that play key roles in brain damage and repair after ICH.

脑出血（ICH）是一种破坏性的中风亚型，没有有效的治疗。缺乏治疗选择部分导致ICH的病理生理学定义不清。沿着这些路线，尽管老年人脑出血患病率的增加， ICH在很大程度上仍然是个谜。为了解决这一关键的知识差距，提出了两个具体目标。目标1：确定脑出血后脑蛋白质组的年龄诱导变化。目的2：确定年龄诱导的脑出血后小胶质细胞和脑浸润性单核细胞源性巨噬细胞（BMDM）蛋白水平的变化。的拟议的研究采用ICH的临床前模型，包括无偏倚和严格的蛋白质组学方法如无标记和TMT标记质谱法和生物信息学方法。成功完成该项目将确定新的分子调节剂，以改善脑出血后的神经系统结果，老人此外，这些研究将首次定义急性分离的小胶质细胞的蛋白质组学特征，巨噬细胞，在脑出血后的脑损伤和修复中发挥关键作用的细胞。