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 George H De Vries 标题 促进脱髓鞘疾病功能恢复 关键词 Exp。自身免疫性脑病。 MS，脱髓鞘疾病，炎症。目的-脱髓鞘后功能丧失是退伍军人在退伍军人管理局医疗中心寻求治疗的主要问题之一。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，多发性硬化症是影响年轻人的主要脱髓鞘疾病。通常，多发性硬化症开始时会出现一系列的恶化和缓解，最终在几年内演变成一个没有缓解的进行性病程。目前 FDA 的治疗重点是减少恶化的次数和频率。我们的假设是：慢性脱髓鞘的功能恢复可以通过招募中枢神经系统中完整的神经元发芽并恢复丢失通路的功能（神经可塑性）来实现。为了检验这一假设，我们将开发我们实验室开发的慢性局灶性脱髓鞘模型（靶向 EAE-tEAE），该模型导致行为任务的功能丧失，在我们的案例中是熟练的前肢检索任务。通过标记对侧完整的通路并确定标记的纤维试图发芽并通过穿过中线接管失去的功能的程度来评估可塑性。我们的合作者 G. Kartje 博士已成功地将这种可塑性测量方法应用于中风模型中。功能恢复将作为神经可塑性的衡量标准进行评估。拟议研究有三个两个目标： 1. 开发并表征存在持续性免疫介导病变的 t-EAE 模型。 2.评估大鼠康复加丰富环境促进t-EAE后恢复的能力预计本研究的结果将为使用和评估其他增强神经可塑性的策略奠定基础，这些策略与康复相结合将有助于提高神经可塑性。快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 制定更有效的康复策略以促进受脱髓鞘疾病影响的退伍军人的功能恢复是本研究提案的目标，与 VA 患者护理任务高度相关。改进的康复策略和改善的功能恢复结果肯定会改善患有多发性硬化症等脱髓鞘疾病的退伍军人的生活质量。据估计，VA 每年为 20,000 名多发性硬化症患者提供护理。改善生活质量有双重好处，因为它不仅会影响多发性硬化症患者的功能能力，而且功能恢复也会减轻护理人员的负担，并可能导致长期治疗成本的降低。据估计，为多发性硬化症患者提供医疗和护理的费用每年超过 34,000 美元，每人一生的费用为 220 万美元（Whetten-Goldstein、Sloan、Goldstein 和 Kulas，1998 年）。应该指出的是，这一估计不包括无形成本，例如护理人员负担增加和生活质量下降，这些成本可能与功能障碍有关。拟议调查的结果将直接转移到康复策略中，因为结果将提供康复可以增加可塑性并以此方式促进功能恢复的原理证明。