Neurophysiology of Spinal Cord Injury and Treatment

脊髓损伤和治疗的神经生理学

• 批准号: 6859364
• 负责人: FLOYD J. THOMPSON
• 金额: $ 30.14万
• 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/6859364
• 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.

说明(申请人提供)：痉挛是一种与脑和脊髓损伤相关的继发性神经疾病，通常是神经系统损伤后阻碍个人护理和生活方式的最难解决的问题之一。尽管痉挛的治疗已经取得了进展，但关于痉挛的病理生理学基础的基本机制、治疗如何具体解决基本机制以及最终慢性治疗如何影响这些基本过程仍有许多未知之处。本申请中提出的实验解决了这些问题，并来自我们的研究，目的是了解正常反射兴奋性的基本神经生理过程，这些变化在脊髓挫伤后是如何变化的，以及这些变化如何与痉挛的发展相关。使用实验性中胸挫伤显示了显著的神经生理学、运动学、神经肌肉和组织学变化，证实了在实验室模型中复制人类痉挛的显著特征的可行性。在这些研究中开发的两种特别灵敏的定量工具(速率抑制的神经生理学分析和速度相关的踝关节扭矩分析)现在可以与行为和组织学研究结合使用，作为一种多学科分析，进一步量化损伤和实验治疗所产生的变化。因此，这项建议的目的是为了更好地了解痉挛造成的长期功能障碍，以及使用运动锻炼和抗痉挛药物(鞘内巴氯芬)(在痉挛模式确定之前开始)进行早期干预治疗的可能性，以影响痉挛和自愿运动活动的长期结果测量。另一个目标是评估慢性鞘内巴氯芬治疗诱导的可塑性的可逆性。接近。这些研究将比较治疗和未治疗的动物在中胸段脊髓挫伤后的神经生理和行为结果。治疗将包括自行调整速度的活动轮运行和持续输注巴氯芬，独立实施，并作为利用急性和亚慢性损伤到治疗间隔的综合治疗，以启动对这些治疗的安全性、可行性和治疗窗口的理解。