Novel Optical Imaging Approach to Study Neurovascular Coupling System

研究神经血管耦合系统的新型光学成像方法

基本信息

批准号：
10528336
负责人：
Lingyan Shi
金额：
$ 43.45万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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：
2022-09-21 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10528336
关键词：
Affect Age Animal Model Biological Assay Blood - brain barrier anatomy Blood Vessels Blood flow Brain Calcium Cells Cerebrovascular system Cerebrum Chemicals Color Cre lox recombination system Data Development Disease Drug Delivery Systems Endothelial Cells Endothelium Event Fluorescence Future Genetic Engineering Goals Homeostasis Image In Vitro Knowledge Label Lead Length Link Measurement Measures Mediating Methodology Methods Microscopy Molecular Multiphoton Fluorescence Microscopy Mus Nerve Degeneration Neurons Nutrient Pathway interactions Perfusion Permeability Photobleaching Procedures Property Proteins Research Personnel Resolution Second Messenger Systems Secondary to Sensory Signal Transduction Signaling Molecule Stimulus Structure System Tight Junctions Time Tissues Vascular Endothelial Cell Vibrissae blood vessel development blood-brain barrier permeabilization calcium indicator experimental study extracellular fluorescence imaging imaging approach imaging modality improved in vivo in vivo imaging in vivo optical imaging innovation molecular imaging mouse genetics mouse model multi-photon neurotransmission neurovascular coupling novel optical imaging postnatal postnatal development protein phosphatase inhibitor-2 quantitative imaging relating to nervous system response solute spatiotemporal two-photon ultrasound vibration

项目摘要

Understanding the relationship between neural activity and Blood-brain barrier (BBB) permeability is important to integrate our knowledge of neurovascular coupling system. Although much effort is focused in understanding the underlying mechanisms that regulate blood flow in response to neural activity5, little is known about how neural activity regulates tissue perfusion. Direct in vivo measurements of Ca2+ dynamics in cerebral blood vessel cells and quantification of BBB permeability have been difficult largely due to technical limitation. Researchers have been using bulky fluorescence-labeled solutes for conventional studies on BBB permeability. However, bulky fluorescence labeling perturbs the structural and functional properties of the biomolecules and suffered from photo bleaching. For these reasons, tiny Raman tagged molecules combined with SRS imaging is ideal for studying BBB permeability in vivo. Here we propose a novel optical imaging approach to determine the relationship between neural activity and BBB permeability in vivo. The main thrust of this proposal is to use a combination of bioorthogonal probed stimulated Raman scattering (SRS), multi-photon fluorescence, and mouse genetics to obtain simultaneous measurements of Ca2+ activity and BBB permeability. Vascular endothelial cells will be labeled with a genetically encoded calcium indicator while bioorthogonal-tagged molecules with specific vibrational modes will be injected into the brain vasculature to measure the BBB permeability, and the relationship between calcium dynamics and permeability of the BBB will be studied. Successful completion of the aims described in this proposal will enable a novel framework for future mechanistic studies of in vivo BBB permeability in animal models for blood vessel development and vasculature diseases.

了解神经活动与血脑屏障（BBB）渗透率之间的关系整合我们对神经血管耦合系统的知识很重要。虽然付出了很多努力专注于理解调节血流的基本机制神经活动5，关于神经活动如何调节组织灌注的知之甚少。直接体内测量大脑血管细胞中Ca2+动力学的测量和BBB的定量渗透性很难在很大程度上是由于技术限制。研究人员一直在使用大量的荧光标记溶质，用于用于BBB渗透性的常规研究。但是，笨重荧光标记的生物分子的结构和功能特性使受到照片漂白的困扰。由于这些原因，小拉曼标记了分子 SRS成像是研究体内BBB渗透性的理想选择。在这里，我们提出了一种新颖的光学成像方法以确定神经活动与BBB渗透性之间的关系体内。该提案的主要目的是使用刺激的生物正交探测的组合拉曼散射（SRS），多光子荧光和小鼠遗传学以同时获得 Ca2+活性和BBB渗透性的测量。血管内皮细胞将被标记具有遗传编码的钙指示剂，而生物正交标记的分子具有特定的振动模式将被注入大脑脉管系统中，以测量BBB渗透性，将研究钙动力学和BBB的渗透性之间的关系。成功完成本提案中描述的目标将使一个新颖的框架动物模型中体内BBB渗透性的未来机械研究发育和脉管系统疾病。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bioorthogonal Stimulated Raman Scattering Imaging Uncovers Lipid Metabolic Dynamics in Drosophila Brain During Aging.

DOI：
10.1089/genbio.2023.0017
发表时间：
2023-06
期刊：
GEN biotechnology
影响因子：
0
作者：
Yajuan Li;Phyllis Chang;Shriya Sankaran;Hongje Jang;Yuhang Nie;Audrey Zeng;Sahran Hussain;Jane Y. Wu;Xu-Qiao Chen;Lingyan Shi
通讯作者：
Yajuan Li;Phyllis Chang;Shriya Sankaran;Hongje Jang;Yuhang Nie;Audrey Zeng;Sahran Hussain;Jane Y. Wu;Xu-Qiao Chen;Lingyan Shi