Neurophysiology of Spinal Cord Injury and Treatment

脊髓损伤和治疗的神经生理学

• 批准号: 6775070
• 负责人: FLOYD J. THOMPSON
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6775070
• 关键词: behavior test; behavioral /social science research tag; chordate locomotion; chronic disease /disorder; combination therapy; disease /therapy duration; electromyography; exercise; functional ability; gait; immunocytochemistry; laboratory rat; muscle relaxants; nervous system disorder chemotherapy; neural plasticity; neuromuscular system; nonhuman therapy evaluation; pathologic process; reflex; rehabilitation; spastic paralysis; spinal cord injury

DESCRIPTION (provided by applicant): Spasticity is a secondary neurological condition associated with brain and spinal cord injury that is often one of the most difficult problems that encumbers the care and lifestyle of individuals following nervous system injury. Although progress has been made in the therapeutic treatment of spasticity, many unknowns remain regarding fundamental mechanisms that underlie the pathophysiology of spasticity, how treatments specifically address fundamental mechanisms, and ultimately, how chronic treatments impact these fundamental processes. The experiments proposed in this application address these issues and have come out of our studies aimed at understanding fundamental neurophysiological processes that underlie normal reflex excitability, how these change following contusion spinal cord injury, and how these changes correlate with the development of spasticity. Use of the experimental midthoracic contusion injury revealed significant neurophysiological, locomotor, neuromuscular, and histological changes that confirm the feasibility of reproducing significant features of human spasticity in a laboratory model. Two particularly sensitive quantitative tools that were developed during these studies (neurophysiological analysis of rate-depression and analysis of velocity-dependent ankle torque) can now be used in conjunction with behavioral and histological study as a multidisciplinary assay to further quantitate changes produced by injury and experimental treatments. Therefore, the objectives of this proposal are to obtain a better understanding of the long term functional disability imposed by spasticity, and the potential for early intervention therapy using locomotor exercise and antispastic medication (intrathecal baclofen) (initiated before spastic patterns are firmly established) to influence long term outcome measures of spasticity and voluntary motor activity. An additional objective is to evaluate the reversibility of plasticity induced by chronic intrathecal baclofen treatment. Approach. These studies will compare neurophysiological and behavioral outcome measures in treated and untreated animals following midthoracic spinal cord contusion injuries. Treatments will consist of self-paced activity wheel running and constant infusion intrathcal baclofen, administered independently and as combined therapies utilizing both acute and subchronic injury-to-treatment intervals to initiate an understanding of safety, feasibility, and therapeutic window for these treatments.

描述（由申请人提供）：痉挛是与大脑和脊髓损伤相关的次要神经系统疾病，这通常是紧张神经系统损伤后患者的护理和生活方式的最困难问题之一。尽管在痉挛的治疗治疗方面取得了进展，但在基本机制的基本机制方面仍然存在许多未知数，这些机制是痉挛的病理生理学，治疗方法如何专门解决基本机制，以及最终如何影响慢性治疗方法如何影响这些基本过程。本申请中提出的实验解决了这些问题，并从我们的研究中提出，旨在理解基本的神经生理过程，这些过程是正常反射兴奋性的基础，这些兴奋性后这些变化如何变化以及这些变化与痉挛的发展如何相关。实验性胸腔挫伤损伤的使用显示出明显的神经生理学，运动，神经肌肉和组织学变化，这些变化证实了在实验室模型中重现人类痉挛的重要特征的可行性。这些研究期间开发的两种特别敏感的定量工具（对速度抑制的神经生理学分析和速度依赖性踝关节扭矩的分析）现在可以与行为和组织学研究一起使用，作为多学科研究，作为多学科测定法，以进一步量化受伤和实验治疗所产生的变化。因此，该提案的目的是更好地了解痉挛性施加的长期功能残疾，以及使用运动运动和消毒剂药物（鞘内baclofen）（牢固地确定痉挛性模式开始）的早期干预治疗的潜力，以影响长期的痉挛性结局和自愿运动活性。另一个目标是评估慢性鞘内巴氯芬治疗引起的可塑性的可逆性。方法。这些研究将比较胸腔中期脊髓挫伤损伤后治疗和未经治疗的动物的神经生理和行为结局指标。治疗将包括自定进度的活动轮运行和恒定输注术中巴氯芬，独立施用，并使用急性和亚少克损伤间隔间隔进行治疗，以启动对安全性，可行性和治疗窗口的理解。