Bringing CLARITY to EAE

为 EAE 带来清晰度

• 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
• 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

 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（由申请人提供）：多发性硬化症（MS）是一种中枢神经系统（CNS）的神经退行性脱髓鞘疾病。实验性自身免疫性脑脊髓炎（EAE）是MS最广泛使用的动物模型，已被广泛用于了解MS中的疾病机制。EAE中的神经病理学研究已通过组织病理学发现炎症、脱髓鞘、神经元和突触损失，这是MS中发现的重演。然而，这些观察是基于脑和脊髓的稀疏采样，没有一个完整的评价这些过程在整个中枢神经系统。在完整的CNS上以3D方式评估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。 Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel（透明脂质交换丙烯酰胺杂交刚性成像兼容组织水凝胶）是最近开发的一种光学透明技术，可对整个CNS进行完整成像。这种方法将CNS嵌入多孔基质中，为蛋白质、核酸和小分子提供结构完整性， 而不结合脂质。然后去除脂质，最终得到光学透明的CNS，其可以容易地可视化并且容易地使用常用技术进行探测。 我们建议在整个中枢神经系统的背景下，使用清晰度检查白色和灰质病理。我们将把这项分析与磁共振成像（MRI）相关联，以确定GM萎缩与其潜在神经病理学之间的关系。