Bringing CLARITY to EAE

 描述(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中应用最广泛的动物模型，已被广泛用于了解MS的发病机制。EAE的神经病理学研究发现，组织病理学发现炎症、脱髓鞘、神经元和突触丢失，但这些观察是基于对大脑和脊髓的稀疏采样，而不是对整个中枢神经系统这些过程的完整评估。在完整的中枢神经系统中以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。透明脂交换丙烯酰胺杂化硬质组织水凝胶(CRILAY)是最近开发的一种光学透明技术，可以完整地对整个中枢神经系统进行成像。这种方法将CNS嵌入到为蛋白质、核酸和小分子提供结构完整性的多孔基质中， 同时让脂类自由流动。然后去除脂质，最终形成光学清晰的中枢神经系统，可以很容易地看到并使用常用的技术进行探测。我们建议在整个中枢神经系统的情况下，使用Clarity来检查白质和灰质病理。我们将把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之间的关系。

 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.