Neuroimaging and neuroprotection of primary oligodendrogliopathy

原发性少突胶质细胞病的神经影像学和神经保护

• 批准号: 7530836
• 负责人: SUBRAMANIAM SRIRAM
• 金额: $ 17.96万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7530836
• 关键词: Animals; Antigens; Apoptotic; Area; Autoimmune Diseases; Autoimmune Process; Autoimmune Responses; Axon; Brain; Cellular Infiltration; Cessation of life; Characteristics; Chelating Agents; Deferoxamine Methanesulfonate; Demyelinations; Genes; Immunosuppressive Agents; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Iron; Lesion; Lymphocyte; Magnetic Resonance Imaging; Mediating; Methods; Modeling; Multiple Sclerosis; Multiple Sclerosis Lesions; Myelin; Neurologic; Neuroprotective Agents; Oligodendroglia; Pathologic; Pathway interactions; Pharmaceutical Preparations; Phase; Range; Rattus; Refractory; Rodent; Spinal Cord; Standards of Weights and Measures; T-Lymphocyte; Techniques; Testing; Thinking; United States Food and Drug Administration; central nervous system demyelinating disorder; disability; dorsal column; environmental agent; immunoregulation; neuroimaging; neuroprotection; novel; pathogen; prevent; white matter

DESCRIPTION (provided by applicant): Multiple Sclerosis is the most common demyelinating disease of the central nervous system. MS is considered to be an autoimmune disease that is triggered by an environmental agent, most likely a pathogen. Destruction of oligodendrocytes and loss of integrity of the underlying axons, form the core pathologic features of MS. Apoptotic death of oligodendrocytes, also referred to as primary oligodendrogliopathy, is seen in approximately 40% of MS lesions and is believed to be the cause of progressive neurological disability. There is considerable need to develop a model of primary oligodendrogliopathy, since this type of destruction of oligodendrocytes is not amenable to conventional therapies. We also need to develop appropriate neuroimaging strategies that can distinguish and quantify inflammatory and non-inflammatory mechanisms of demyelination. We plan to examine a novel model of primary oligodendrogliopathy which is induced by the injection of LPS into CNS white matter. We propose that this model more likely represents the underpinnings of CNS demyelination in the prototypic type III lesion. This model of CNS demyelination will provide an opportunity to examine the sensitivity of a range of established and novel MRI techniques to distinguish inflammatory and non-inflammatory pathways and examine the efficacy of neuroprotective agents in blunting the progression of the non- inflammatory demyelinating lesions. This study opens the way to examine the loss of myelin in the brain using novel MRI techniques. Also, it explores the use of new drugs to prevent and reverse myelin injury.

描述(申请人提供)：多发性硬化症是最常见的中枢神经系统脱髓鞘疾病。多发性硬化症被认为是一种自身免疫性疾病，由环境因素触发，最有可能是病原体。少突胶质细胞的破坏和轴突完整性的丧失构成了MS的核心病理特征。少突胶质细胞的凋亡性死亡，也被称为原发性少突胶质细胞病，见于大约40%的MS病变，被认为是进行性神经功能障碍的原因。发展一种原发少突胶质细胞病的模型是相当有必要的，因为这种类型的少突胶质细胞破坏不符合传统疗法。我们还需要开发适当的神经成像策略，以区分和量化脱髓鞘的炎性和非炎性机制。我们计划研究一种新的原发少突胶质细胞病变模型，这种疾病是由中枢神经系统白质内注射脂多糖引起的。我们认为，该模型更有可能代表典型III型病变中中枢神经系统脱髓鞘的基础。这种中枢神经系统脱髓鞘模型将提供一个机会，以检查一系列成熟的和新的MRI技术的敏感性，以区分炎性和非炎性途径，并检查神经保护剂在钝化非炎症性脱髓鞘损害进展方面的有效性。这项研究为使用新的核磁共振技术检查大脑中髓鞘的丢失开辟了道路。此外，它还探索使用新药来预防和逆转髓鞘损伤。