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Inflammatory changes and glymphatic dysfunction in carbon monoxide neuropathology

一氧化碳神经病理学中的炎症变化和类淋巴功能障碍

基本信息

批准号：
10576369
负责人：
STEPHEN RAYMOND THOM
金额：
$ 58.66万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
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：
2022-03-01 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10576369
关键词：
Acute Adherence Animal Model Animals Antioxidants Astrocytes Biochemical Blood Blood Circulation Blood Vessels Blood specimen Brain Brain Injuries Carbon Monoxide Carbon Monoxide Poisoning Carboxyhemoglobin Cells Cerebrospinal Fluid Cerebrovascular system Cerebrum Cessation of life Cognitive Data Demyelinations Diameter Dose Event Excision Exhibits Fluorescence Microscopy Functional disorder Glial Fibrillary Acidic Protein Goals Hospitals Hypoxia Image Immune Tolerance Inflammasome Inflammation Inflammatory Inflammatory Response Infusion procedures Injections Injury Knockout Mice Lead Liquid substance Lymphatic Magnetic Resonance Imaging Mediating Methods Modification Morbidity - disease rate Mus Myelin Basic Proteins Neuroglia Neurologic Neurologic Deficit Neutropenia Neutrophil Activation Oxidative Stress Pathologic Pathway interactions Patients Peptide Hydrolases Periodicity Peroxidases Play Poison Poisoning Process Production Resistance Role Stream Stress Surveys Survivors System Thrombospondin 1 Vesicle Visit adaptive immune response adverse outcome aquaporin 4 biological adaptation to stress cerebral microvasculature glymphatic dysfunction glymphatic flow glymphatic function glymphatic system meter minimally invasive mitochondrial dysfunction motor impairment mouse model neuroinflammation neuropathology neutrophil nitrosative stress novel p65 particle response transmission process wasting water channel white matter change

项目摘要

ABSTRACT This project is to elucidate the role of inflammation and perturbations of the brain glial-based lymphatic (glymphatic) pathway in carbon monoxide (CO)-induced brain injuries. Based on preliminary data we hypothesize that astrocyte-derived microparticles (MPs) expressing thrombospindin-1 play a causal role in CO-induced neuropathology that includes glymphatic dysfunction. Further, once these MPs are liberated to the bloodstream they activate circulating neutrophils that sequester along the neurovasculature to exacerbate inflammation, leading to functional neurological deficits. Specific aims are: (1) Assess glymphatic function in response to CO in mice by MRI and fluorescence microscopy; (2) Identify the role of glymphatic outflow to CO-neuropathology in mice; (3) Determine the relationship of neuroinflammation and glymphatic dysfunction to functional deficits; (4) Evaluate associations of morbidity in CO poisoned patients with MPs elevations and intra-particle pro-inflammatory agents.

摘要本项目旨在阐明炎症和扰动脑胶质细胞的作用，淋巴（胶质淋巴）途径在一氧化碳（CO）诱导的脑损伤。基于初步数据我们假设星形胶质细胞衍生的微粒（MP）表达血栓素-1在CO诱导的神经病理学中起因果作用，功能障碍此外，一旦这些MP被释放到血液中，中性粒细胞，其沿着神经血管沿着隔离以加剧炎症，导致功能性神经缺陷具体目标是：（1）评估胶质淋巴功能，通过MRI和荧光显微镜观察小鼠CO;（2）确定胶质淋巴流出对（3）确定神经炎症与胶质淋巴细胞增生的关系（4）评价CO中毒患者发病率的相关性 MP升高和颗粒内促炎剂。