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：
10441964
负责人：
STEPHEN RAYMOND THOM
金额：
$ 61.47万
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/10441964
关键词：
Acute Adherence Animal Model Animals Antioxidants Astrocytes Biochemical Blood Blood Circulation Blood specimen Brain Brain Injuries Caliber Carbon Monoxide Carbon Monoxide Poisoning Carboxyhemoglobin Cells Cerebrospinal Fluid Cerebrovascular system Cerebrum Cessation of life Cognitive Data Demyelinations 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 Patients Peptide Hydrolases Periodicity Peroxidases Play Poisoning Process Production Resistance Role Stream Stress Surveys Survivors Thrombospondin 1 Vesicle Visit adaptive immune response adverse outcome aquaporin 4 base biological adaptation to stress cerebral microvasculature foot glymphatic dysfunction glymphatic flow glymphatic function glymphatic system minimally invasive mitochondrial dysfunction motor impairment mouse model neuroinflammation neuropathology neutrophil nitrosative stress novel p65 particle response 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.

抽象的该项目旨在阐明炎症和神经胶质细胞扰动的作用一氧化碳（CO）引起的脑损伤中的淋巴（类淋巴）途径。基于初步数据我们假设星形胶质细胞衍生的微粒（MP）表达 thrombospindin-1 在 CO 诱导的神经病理学（包括类淋巴神经病理学）中发挥因果作用功能障碍。此外，一旦这些 MP 被释放到血液中，它们就会激活循环中性粒细胞沿着神经血管隔离，加剧炎症，导致功能性神经缺陷。具体目标是： (1) 评估类淋巴功能通过 MRI 和荧光显微镜观察小鼠体内的 CO； (2) 确定类淋巴流出对小鼠的协同神经病理学； (3)确定神经炎症与类淋巴系统的关系功能障碍到功能缺陷； (4) 评估一氧化碳中毒患者发病率的关联 MPs 升高和颗粒内促炎剂。