Bringing CLARITY to EAE

为 EAE 带来清晰度

基本信息

批准号：
9247856
负责人：
Allan James MacKenzie-Graham
金额：
$ 33.69万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9247856
关键词：
Acrylamides Anatomy Animal Model Area Atrophic Brain Brain imaging Brain region Cerebral cortex Clinical Data Data Set Demyelinations Development Diffuse Dimensions Disease Disease Progression Evaluation Event Experimental Autoimmune Encephalomyelitis Goals Histology Histopathology Hybrids Hydrogels Image Immune Immunohistochemistry Impaired cognition Inflammation Label Laboratories Lead Lesion Lipids Literature Magnetic Resonance Imaging Measures Methodology Modality Multiple Sclerosis Mus Nerve Degeneration Neuraxis Neurons Nucleic Acids Optical Methods Optics Pathogenesis Pathology Pattern Pharmaceutical Preparations Population Process Proteins Resolution Role Sampling Spinal Cord Stains Structure Synapses Techniques Technology Three-Dimensional Imaging Time Tissue Stains Tissues base cellular imaging central nervous system demyelinating disorder cerebral atrophy disability gray matter high resolution imaging human disease in vivo interest light scattering neuropathology public health relevance reconstruction regional atrophy small molecule white matter

项目摘要

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a neurodegenerative, demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS, has been used extensively to understand disease mechanisms in MS. Neuropathological studies in EAE have found inflammation, demyelination, neuronal and synaptic loss by histopathology, a recapitulation of findings in MS. However, these observations are based on sparse sampling of the brain and spinal cord, not a complete evaluation of these processes throughout the entire CNS. The ability to evaluate these processes in 3D across an intact CNS would be enormously helpful for evaluating their true extent in disease. Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) is a recently developed optical clearing technology that permits the intact imaging of the entire CNS. This approach embeds the CNS in a porous matrix that provides structural integrity to proteins, nucleic acids, and small molecules, while leaving lipids unbound. The lipids are then removed, culminating in an optically cleared CNS that can be easily visualized and easily probed using commonly available techniques. We propose to use CLARITY to examine white and gray matter pathology in the context of the entire CNS. We will correlate this analysis with magnetic resonance imaging (MRI) to determine the relationship between GM atrophy and its underlying neuropathologies.

描述（通过应用提供）：多发性硬化症（MS）是一种神经退行性，中枢神经系统（CNS）的脱髓鞘疾病。实验性自身免疫性脑脊髓炎（EAE）是使用最广泛的MS动物模型，已广泛用于了解MS中的疾病机制。 EAE中的神经病理学研究发现，通过组织病理学注射，脱髓鞘，神经元和突触丧失，对MS的发现的概括。但是，这些观察结果是基于对大脑和脊髓的稀疏采样，而不是整个中枢神经系统中这些过程的完整评估。在完整的中枢神经系统中评估3D中这些过程的能力将极大地有助于评估它们在疾病中的真实程度。透明脂质交换的丙烯酰胺杂交刚性成像组织 - 凝胶凝胶（Clarity）是一种最近开发的光学清除技术，可允许整个CNS的完整成像。这种方法将CNS嵌入多孔基质中，该基质为蛋白质，核酸和小分子提供结构完整性，在离开脂质的同时未结合。然后卸下脂质，在光学清除的中枢神经系统中达到顶点，可以轻松地使用常用技术可视化并易于探测。我们建议在整个中枢神经系统的背景下使用清晰度检查白质病理学。我们将将这一分析与磁共振成像（MRI）相关联，以确定GM萎缩与其潜在神经病理学之间的关系。