Particulate Matter-Induced Pulmonary Exosomes and the Lung-Brain Axis
颗粒物诱导的肺外泌体和肺脑轴
基本信息
- 批准号:10302568
- 负责人:
- 金额:$ 22.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-16 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAgingAir PollutionAirborne Particulate MatterArsenicAutomobile DrivingBiologicalBiomedical ResearchBirthBlood - brain barrier anatomyBlood VesselsBrainCarbon BlackCaveolaeCell CommunicationCellsChildClathrinCohort StudiesDataDietDiseaseDustEndocytosisEndothelial CellsEndotheliumEnvironmentEnvironmental ExposureEnvironmental WindExposure toF-ActinFunctional disorderGasesGeneral PopulationGenetic TranscriptionHealthHealth SciencesHealth ServicesHealth Services AccessibilityHeavy MetalsHomeHomeostasisIn VitroIndividualInflammatoryInhalationInjectionsInstitutesKnowledgeLeadLifeLinkLungMagnetic Resonance ImagingMediatingMental disordersMetalsMusNative AmericansNavajoNeurologicNew MexicoNickelOntologyOutcomeParticulateParticulate MatterPathologicPeptide FragmentsPopulationRNARecording of previous eventsResearchResearch PersonnelResearch ProposalsResource SharingRoleSerumSignal TransductionSiteSocioeconomic FactorsSouthwestern United StatesStrokeSubstance abuse problemTailTestingUnited States National Institutes of HealthUniversitiesUraniumVanadiumVascular DementiaVascular DiseasesVeinsVesicleair filterair quality regulationbasebehavioral healthblood-brain barrier disruptionbrain healthcellular imagingcerebrovascularendothelial dysfunctionexosomefine particleshigh rewardhigh riskin vivonervous system disorderneuroimagingneuroinflammationneurovascularremediationresponsesocialsuccesstribal community
项目摘要
PROJECT SUMMARY AND ABSTRACT
Corporate uranium mines were established in the Southwestern United States from the 1940s-1980s, leaving
behind poorly remediated sites near surrounding residential homes. Inhaled, mine-site derived particulate matter
(PM) has been associated with an increase in serum inflammatory potential and subsequent vascular and
neurological disease. The PM arising from these uranium mines tends to be high in specific toxic, inorganic
metals including vanadium (V), uranium (U), and often nickel (Ni) and arsenic (As). The full scope of systemic
health effects following inhaled mine-site derived PM is unknown, but such inflammatory impacts to the
neurovasculature could promote neurological diseases and the elucidation of such mechanisms has yet to be
discerned. Therefore, the primary objective of this research proposal is to develop a deeper understanding of
the mechanistic, causal basis for mine-site derived PM-induced neurovascular dysfunction. In preliminary
studies, we have observed that mine site PM is more acutely toxic to the lungs and brain compared to regional
background PM. Furthermore, similar studies of inhaled particulates and gases demonstrate a BBB dysfunction
that can drive neuroinflammatory outcomes. Therefore, my specific aims will serve two primary objectives: 1)
mechanistically delineate the contribution of circulating PM-induced exosomes as drivers of cerebrovascular
endothelial barrier dysfunction and neuroinflammation. 2) quantitatively assess endothelial cell dynamics
following treatment with circulating exosomes from PM-exposed mice using high-content, single-cell imaging.
This proposal will serve as a high-risk, high reward project in a supportive academic environment where
investigators can take advantage of several shared resources. We will take full advantage of the outstanding
facilities at the University of New Mexico Health Sciences Center, including the Brain and Behavioral Health
Institute (BBHI) and the Biomedical Research and Integrative Neuroimaging Center (BRaIN), where the MRI, is
housed. Data from these studies will ultimately lead to essential information pertinent to Southwestern
populations in close proximity to abandoned uranium mines, as well as governing agencies involved in air-quality
regulations.
项目摘要和摘要
从1940年代1980年代开始,在美国西南部建立了铀矿业
在住宅周围房屋附近的补救局局部遗址不佳的后面。吸入,矿场衍生的颗粒物
(PM)与血清炎症潜力和随后的血管的增加有关
神经疾病。这些铀矿引起的PM往往在特定的有毒,无机上很高
金属包括钒(V),铀(U),以及镍(Ni)和砷(AS)。全身范围
吸入矿场衍生的PM后的健康效应尚不清楚,但是这种炎症对
神经血管口可以促进神经疾病,这种机制的阐明尚未
辨别。因此,这项研究建议的主要目的是对
矿场衍生PM诱导的神经血管功能障碍的机械性,因果关系。在初步
研究,我们已经观察到,与区域相比
背景下午。此外,对吸入的颗粒物和气体的类似研究表现出BBB功能障碍
这可以推动神经炎症结果。因此,我的具体目标将达到两个主要目标:1)
机械师将循环PM诱导的外泌体的贡献描述为脑血管的驱动因素
内皮屏障功能障碍和神经炎症。 2)定量评估内皮细胞动力学
使用高含量的单细胞成像从暴露于PM暴露小鼠的外泌体进行处理后。
该建议将在支持性的学术环境中作为一个高风险,高奖励项目
调查人员可以利用几个共享资源。我们将充分利用杰出的
新墨西哥大学健康科学中心的设施,包括大脑和行为健康
MRI为
安置。这些研究的数据最终将导致与西南有关的基本信息
靠近废弃铀矿的人口以及参与空气质量的机构
法规。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Katherine Zychowski其他文献
Katherine Zychowski的其他文献
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{{ truncateString('Katherine Zychowski', 18)}}的其他基金
Systemic Implications and Novel Mechanisms of Circulating Extracellular Vesicles Following Inhaled Exposures
吸入暴露后循环细胞外囊泡的系统影响和新机制
- 批准号:
10733648 - 财政年份:2023
- 资助金额:
$ 22.73万 - 项目类别:
Particulate Matter-Induced Pulmonary Exosomes and the Lung-Brain Axis
颗粒物诱导的肺外泌体和肺脑轴
- 批准号:
10451822 - 财政年份:2021
- 资助金额:
$ 22.73万 - 项目类别:
Neurovascular Consequences of Inhaled Uranium Mine-Site Dust Exposure
吸入铀矿场粉尘暴露对神经血管的影响
- 批准号:
10164782 - 财政年份:2020
- 资助金额:
$ 22.73万 - 项目类别:
Neurovascular Consequences of Inhaled Uranium Mine-Site Dust Exposure
吸入铀矿场粉尘暴露对神经血管的影响
- 批准号:
10094731 - 财政年份:2020
- 资助金额:
$ 22.73万 - 项目类别:
Neurovascular Consequences of Inhaled Uranium Mine-Site Dust Exposure
吸入铀矿场粉尘暴露对神经血管的影响
- 批准号:
10392427 - 财政年份:2020
- 资助金额:
$ 22.73万 - 项目类别:
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