CRCNS US-German Research Proposal: Computational modeling and real-time visualization of microscale-forces-induced neurovascular unit permeability

CRCNS 美德研究提案:微尺度力诱导的神经血管单元渗透性的计算建模和实时可视化

基本信息

  • 批准号:
    2207804
  • 负责人:
  • 金额:
    $ 46.28万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-12-01 至 2025-11-30
  • 项目状态:
    未结题

项目摘要

The blood vessels in the central nervous system fulfill the complicated task of providing oxygen and nutrients to the neurons, while at the same time protecting the neurons from harmful molecules. This is accomplished through tight opposition and closure of the cells that cover the inner surfaces of these vessels. How these cells respond to microscale mechanical vibrations is a mystery. Such vibrations occur when sound waves that are too high-pitched to be audible propagate through tissues. Another way to generate microscale vibrations is a brief laser pulse. The goal of this research is to develop a novel technology that creates controlled microscale vibrations, while at the same time microscopically visualizing the effect. The neuronal layer in the back of the eye, the retina, will be used for this study. These experiments will provide for the first time insights into how cells react to mechanical alterations and will open the door to a new category of interventions. It is expected that cells distinguish the pitch and intensity of these microscale mechanical vibrations and gauge their responses accordingly. During normal aging or in diseases, such as Alzheimer’s disease, aberrant molecules accumulate around neurons and impede their normal functioning. Controlled microscale mechanical vibrations bring about new possibilities for dislodging and removing these deleterious molecules before neurons are harmed and the individuals’ cognitive or visual functions decline. The principal investigator will engage with students and educators in the broader community to share the novel technologies under development herein. A goal will be to attract, enroll, and train individuals with disabilities, women, and minorities in this area of research. The Blood-Retina-Barrier (BRB) selectively regulates the permeability of molecules that reach the neurons. There is an unmet scientific and medical need for a temporal and non-injurious opening of the BRB. The goals of this project are A) development of a novel technology to deliver microscale mechanical vibrations to the retina under live microscopy, B) to visualize the effect of these microscale vibrations in the BRB, and C) to computationally model the process of the molecular passage through the BRB. The expected outcome will be image-guided acoustic and/or photo-acoustic alterations of the BRB. The project team's approach combines in vivo animal experiments with computational modeling in silico. To modulate BRB’s permeability, the project team will implement a recently developed new laser-based photo-acoustic and pure acoustic technologies to study the resulting dynamic processes in real-time with an image-guided approach using custom-developed hardware. A computational model will be developed based on mass balance equations. In rodents, BRB permeability will be measured through quantitative analysis of angiographic images. The results of the in vivo experiments will refine the computational modeling.A companion project is being funded by the Federal Ministry of Education and Research, Germany (BMBF). This project is jointly funded by the following NSF programs: Disability and Rehabilitation Engineering and Collaborative Research in Computational Neuroscience.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
中枢神经系统中的血管完成向神经元提供氧气和营养的复杂任务,同时保护神经元免受有害分子的侵害,这是通过覆盖神经元内表面的细胞的紧密对抗和闭合来实现的。当声波太高而无法听到时,这些细胞如何响应微尺度机械振动是一个谜。产生微尺度振动的另一种方法是产生短暂的激光脉冲。研究是为了开发新技术产生受控的微尺度振动,同时在显微镜下观察眼睛后部视网膜的神经层,这些实验将首次深入了解细胞如何反应。机械改变,并将为一类新的干预措施打开大门,预计细胞可以区分这些微尺度机械振动的音调和强度,并相应地测量它们在正常衰老或阿尔茨海默病等疾病中的反应。神经元周围和受控的微尺度机械振动为在神经元受到伤害和个体认知或视觉功能下降之前驱逐和去除这些有害分子带来了新的可能性。这里正在开发的新技术的一个目标是吸引、招募和培训残疾人、女性和少数族裔从事这一研究领域。血液视网膜屏障(BRB)选择性地调节到达的分子的渗透性。神经元。对于暂时且无伤害地打开 BRB 的科学和医学需求尚未得到满足。该项目的目标是 A) 开发一种新技术,在实时显微镜下向视网膜传递微尺度机械振动,B) 使视网膜可视化。 BRB 中这些微尺度振动的影响,以及 C) 对分子通过 BRB 的过程进行计算建模。该项目的预期结果将是图像引导的声学和/或光声改变。该团队的方法将体内动物实验与计算机建模相结合,为了调节 BRB 的渗透性,该项目团队将实施最近开发的基于激光的光声和纯声技术,以通过图像实时研究由此产生的动态过程。 - 使用定制开发的硬件的指导方法将基于质量平衡方程开发计算模型,通过血管造影图像的定量分析来测量 BRB 渗透性。一个配套项目由德国联邦教育和研究部 (BMBF) 资助,该项目由以下 NSF 项目联合资助:残疾与康复工程和计算神经科学合作研究。该奖项反映了 NSF 的法定使命。通过使用基金会的智力价值和更广泛的影响审查标准进行评估,并被认为值得支持。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ali Hafezi-Moghadam其他文献

Ali Hafezi-Moghadam的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

相似国自然基金

Ⅰ型单纯疱疹病毒通过皮层蛋白US3诱导神经元线粒体损伤及其在阿尔茨海默病中的作用
  • 批准号:
    82372245
  • 批准年份:
    2023
  • 资助金额:
    49 万元
  • 项目类别:
    面上项目
基于US介导硫酮氧化的早诊分子探针的制备与应用研究
  • 批准号:
    22377069
  • 批准年份:
    2023
  • 资助金额:
    50 万元
  • 项目类别:
    面上项目
让我们一起线上购物吧!探究影响消费者协同购物效果的因素及其作用机理
  • 批准号:
    72372112
  • 批准年份:
    2023
  • 资助金额:
    40 万元
  • 项目类别:
    面上项目
BoCP: US-China: 榕-蜂共生体系性状创新在增加生物多样性中的贡献
  • 批准号:
    32261123001
  • 批准年份:
    2022
  • 资助金额:
    450 万元
  • 项目类别:
    国际(地区)合作与交流项目
SRS: US-China: 基础设施促进城乡融合可持续发展的驱动机理与决策机制研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    300 万元
  • 项目类别:

相似海外基金

CRCNS US-German Collaborative Research Proposal: Neural and computational mechanisms of flexible goal-directed decision making
CRCNS 美德合作研究提案:灵活目标导向决策的神经和计算机制
  • 批准号:
    2309022
  • 财政年份:
    2024
  • 资助金额:
    $ 46.28万
  • 项目类别:
    Standard Grant
CRCNS US-German Research Proposal - The diversification of retinal ganglion cells: A combined transcriptomic, genome engineering and imaging approach
CRCNS 美国-德国研究提案 - 视网膜神经节细胞的多样化:转录组学、基因组工程和成像相结合的方法
  • 批准号:
    2309039
  • 财政年份:
    2023
  • 资助金额:
    $ 46.28万
  • 项目类别:
    Standard Grant
CRCNS US-German Research Proposal: Quantitative and Computational Dissection of Glutamatergic Crosstalk at Tripartite Synapses
CRCNS 美德研究提案:三方突触谷氨酸能串扰的定量和计算剖析
  • 批准号:
    10612169
  • 财政年份:
    2023
  • 资助金额:
    $ 46.28万
  • 项目类别:
CRCNS US-German Research Proposal: Combining computational modeling and artificial intelligence to understand receptor function in physiology and disease
CRCNS 美德研究提案:结合计算模型和人工智能来了解生理学和疾病中的受体功能
  • 批准号:
    2113030
  • 财政年份:
    2022
  • 资助金额:
    $ 46.28万
  • 项目类别:
    Standard Grant
CRCNS US-German Research Proposal: Efficient representations of social knowledge structures for learning from a computational, neural and psychiatric perspective (RepSocKnow)
CRCNS 美德研究提案:从计算、神经和精神病学角度学习的社会知识结构的有效表示 (RepSocKnow)
  • 批准号:
    10688109
  • 财政年份:
    2022
  • 资助金额:
    $ 46.28万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了