Promotion of Functional Recovery From Demylinating Disease

促进脱髓鞘疾病的功能恢复

• 批准号: 7749915
• 负责人: George Henry De Vries
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7749915
• 关键词: Activities of Daily Living; Address; Affect; Area; Autoimmune Process; Axon; Behavior; Behavioral; Brain; Brain region; Care given by nurses; Caregiver Burden; Caring; Cavia; Chronic; Contralateral; Demyelinating Diseases; Demyelinations; Disease; Disease remission; Environment; Evaluation; Experimental Autoimmune Encephalomyelitis; Fiber; Forelimb; Frequencies; Future; Goals; Immune; Impairment; Individual; Infarction; Infiltration; Inflammation; Inflammatory; Injection of therapeutic agent; Investigation; Ipsilateral; Label; Laboratories; Lead; Lesion; Limb structure; Living Costs; Measures; Mediating; Medical; Medical center; Methods; Middle Cerebral Artery Occlusion; Mission; Modeling; Motor; Multiple Sclerosis; Myelin Basic Proteins; Nerve Degeneration; Neuronal Plasticity; Neurons; Outcome; Pathway interactions; Patient Care; Patients; Plastics; Principal Investigator; Process; Quality of life; Rattus; Recovery; Recovery of Function; Recruitment Activity; Red nucleus structure; Rehabilitation therapy; Research; Research Proposals; Retrieval; Series; Side; Spinal Cord; Stem cells; Stroke; Testing; Therapeutic Effect; Therapeutic Intervention; Time; Training; Treatment Cost; Veterans; Work; base; brain tissue; chronic demyelination; cost; cytokine; experience; functional loss; functional restoration; implantation; improved; life time cost; loss of function; nerve injury; neuronal circuitry; oligodendrocyte-myelin glycoprotein; public health relevance; rehabilitation strategy; repaired; research study; young adult

DESCRIPTION (provided by applicant): Principal Investigator George H De Vries Title Promotion of Functional Recovery From Demyelinating Disease KeyWords Exp. Autoimmune Enceph. MS, Demyelinating Diseases, Inflammation. Purpose- Functional loss after demyelination is a one of the major problems of veterans seeking treatment at VA medical centers. It is estimated that currently there are 20,000 veterans who are actively receiving treatment for multiple sclerosis (MS) which is the major demyelinating disease affecting young adults. Often MS begins as a series of exacerbations and remissions which eventually over a period of years resolves into a progressive course with no remissions. Current FDA treatments are focused on decreasing the number and frequency of exacerbations. Our hypothesis is: Functional recovery from chronic demyelination can be achieved by recruiting intact neurons in the CNS to sprout and restore function to the lost pathways (neuroplasticity). In order to test this hypothesis we will develop a model of chronic focal demyelination (targeted EAE-tEAE) developed in our laboratory which results in the functional loss of a behavioral task in our case a skilled forelimb retrieval task. Plasticity will be evaluated by labeling the contralateral intact pathway and determining the degree to which the labeled fibers attempt to sprout and take over lost function by crossing the midline. This measure of plasticity has been successfully used in the stroke model by our collaborator Dr. G. Kartje. Functional recovery will be evaluated as a measure of neuroplasticity. There are three two objectives for the proposed research: 1. To develop and characterize a t-EAE model in which there is a persistent immune-mediated lesion. 2.To evaluate the ability of the rat rehabilitation plus enriched enviorment to promote recovery after t-EAE It is anticipated that the results of this study will form the basis for the use and evaluation of the other strategies to enhance neuroplasticity which combined with rehabilitation will quickly and effectively promote functional recovery. PUBLIC HEALTH RELEVANCE: Relevance of Proposed Work to the VA Patient Care Mission Developing more effective rehabilitation strategies to promote functional recovery of veterans affected by demyelinating disease is the goal of this research proposal which is highly relevant to the VA patient care mission. Improved rehabilitation strategies with improved functional recovery outcome will certainly improve the quality of life for veterans afflicted with demyelinating disease such as multiple sclerosis. The VA has been estimated to provide care to 20,000 patients with MS each year. There is a double benefit to improved quality of life since it will not only impact the functional ability of the individual with MS, but functional recovery will also reduce the caregiver burden and may lead to a reduction in long-term treatment costs. The cost of providing medical and nursing care to an individual with MS has been estimated at over 34,000 dollars per year, with a per individual lifetime cost of 2.2 million (Whetten-Goldstein, Sloan, Goldstein, & Kulas, 1998). It should be noted that this estimate does not include intangible costs such as increased caregiver burden, and decreased quality of life - costs that may be associated with impairment in functional ability. The results of the proposed investigation will be directly transferrable to rehabilitation strategies since the results will provide a proof of principle that rehabilitation can increase plasticity and in this way promote functional recovery.

描述（由申请人提供）： 首席研究员乔治·德·弗里斯（George H de Vries）从脱髓鞘疾病关键词经验提升功能恢复的头衔。自身免疫性脑。 MS，脱髓鞘疾病，炎症。脱髓鞘后的目的功能损失是在VA医疗中心寻求治疗的退伍军人的主要问题之一。据估计，目前有20,000名退伍军人正在积极接受多发性硬化症（MS）的治疗，这是影响年轻人的主要脱髓鞘疾病。通常，MS是一系列加重和恢复的开始，最终在几年中可以解决渐进式课程，而没有退缩。当前的FDA处理集中在减少加重的数量和频率上。我们的假设是：通过募集中枢神经系统中的完整神经元以发芽并恢复丢失途径（神经可塑性）来实现慢性脱髓鞘的功能恢复。为了检验这一假设，我们将开发一种在我们的实验室中开发的慢性局灶性脱髓鞘模型（有针对性的EAE-TEAE），该模型在我们的情况下导致了行为任务的功能丧失，这是熟练的前肢检索任务。将通过标记对侧完整途径来评估可塑性，并确定标记的纤维试图发芽并通过越过中线接管损失功能的程度。我们的合作者G. Kartje博士在中风模型中成功使用了这种可塑性。功能恢复将被评估为神经可塑性的量度。拟议的研究有三个目标：1。开发和表征T-EAE模型，其中存在持续的免疫介导的病变。 2.评估大鼠康复的能力以及在T-EAE之后促进恢复的丰富环境的能力，预计这项研究的结果将构成使用和评估其他策略以增强神经可塑性的基础，以增强与康复相结合的神经可塑性，将迅速有效地促进功能恢复。 公共卫生相关性： 拟议工作与VA患者护理任务的相关性，制定了更有效的康复策略，以促进受脱后疾病影响的退伍军人的功能恢复，这是该研究建议的目标，它与VA患者护理任务高度相关。改善功能恢复结果的改进恢复策略无疑会改善患有脱髓鞘疾病（例如多发性硬化症）的退伍军人的生活质量。据估计，VA每年为20,000名MS患者提供护理。改善生活质量有双重好处，因为它不仅会影响MS个人的功能能力，而且功能恢复还将减轻护理人员负担，并可能导致长期治疗成本的降低。估计每年超过34,000美元，为MS的个人提供医疗和护理的成本，每人一生的成本为220万美元（Whetten-Goldstein，Sloan，Goldstein，Goldstein和Kulas，1998年）。应当指出的是，此估计不包括无形的成本，例如增加的护理人员负担和减少的生活质量 - 可能与功能能力障碍有关的成本。拟议的调查结果将直接转移到康复策略中，因为结果将提供原则证明，康复可以增加可塑性，并以这种方式促进功能恢复。