Inflammatory changes and glymphatic dysfunction in carbon monoxide neuropathology

摘要 本项目旨在阐明炎症和脑神经胶质细胞紊乱的作用。 一氧化碳(CO)脑损伤的淋巴(淋巴)通路基于 初步数据我们假设星形胶质细胞衍生的微粒(MPS)表达 血栓旋蛋白-1在一氧化碳诱导的包括淋巴疾病在内的神经病理中起因果作用 功能障碍。此外，一旦这些MPS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系统隔离，加剧炎症，导致 功能性神经缺陷。具体目标是：(1)评估淋巴功能以应对 通过MRI和荧光显微镜观察小鼠一氧化碳的变化；(2)确定淋巴流出在 小鼠的共同神经病理学；(3)确定神经炎症与淋巴组织的关系 功能障碍与功能缺陷的关系；(4)评估一氧化碳中毒患者发病率的相关性 有MPS升高和颗粒内促炎剂。

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.