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Neurophysiology of Spinal Cord Injury and Treatment

脊髓损伤和治疗的神经生理学

基本信息

批准号：
7194255
负责人：
FLOYD J. THOMPSON
金额：
$ 28.58万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7194255
关键词：
Action Potentials Acute Address Animals Ankle Anoxia Baclofen Behavioral Biological Assay Brain Candy Caring Cereals Chest Chronic Collaborations Combined Modality Therapy Condition Contusions Daily Data Development Early Intervention Environment Exercise Fatigue Ferns Functional disorder Gait Glutamates Goals H-Reflex Hindlimb Human Hyperreflexia Hyporeflexia Individual Infusion procedures Injury Laboratories Life Style Limb structure Locomotion Locomotor Recovery Lower Extremity Lumbar spinal cord structure Measures Mental Depression Modeling Morphology Motor Activity Motor Neurons Muscle Nervous System Trauma Neurologic Noise Optic Nerve Outcome Measure Pathway interactions Pattern Performance Pharmaceutical Preparations Phase Process Race Rain Rate Rattus Recovery Reflex action Relative (related person)Reporting Risk Running Safety Score Shapes Signal Transduction Spastic Spinal Cord Spinal Cord Contusions Spinal cord injury Study models Testing Therapeutic Therapeutic Intervention Time Torque Training Walking Week Weight-Bearing state base day excitotoxicity functional disability gamma-Aminobutyric Acid human study improved injured monosynaptic reflex multidisciplinary neurophysiology research study size stretch reflex tool white matter

项目摘要

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）：痉挛是一种与脑和脊髓损伤相关的继发性神经系统疾病，通常是神经系统损伤后患者护理和生活方式中最困难的问题之一。虽然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，仍然存在许多未知数。本申请中提出的实验解决了这些问题，并且已经从我们的研究中得出，这些研究旨在理解作为正常反射兴奋性基础的基本神经生理过程，这些过程在挫伤性脊髓损伤后如何变化，以及这些变化如何与痉挛的发展相关。使用的实验性胸中部挫伤损伤揭示了显着的神经生理学，运动，神经肌肉，和组织学的变化，证实了在实验室模型中再现人类痉挛的显着特征的可行性。在这些研究中开发的两种特别敏感的定量工具（心率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结合使用，作为多学科分析，以进一步定量损伤和实验治疗产生的变化。因此，本提案的目的是更好地了解痉挛状态造成的长期功能障碍，以及使用运动锻炼和解痉挛药物（鞘内巴氯芬）（在痉挛模式牢固建立之前开始）进行早期干预治疗以影响痉挛状态和自主运动活动的长期结局指标的可能性。另一个目的是评估慢性鞘内巴氯芬治疗诱导的可塑性的可逆性。Approach.这些研究将比较胸中段脊髓挫伤后治疗和未治疗动物的神经生理学和行为结局指标。治疗将包括自主活动轮运行和持续输注皮内巴氯芬，独立给药和联合治疗，利用急性和亚慢性损伤至治疗间隔，以开始了解这些治疗的安全性、可行性和治疗窗。