Motoneuron pool plasticity following spinal cord injury

脊髓损伤后运动神经元池可塑性

• 批准号: 8632685
• 负责人: THOMAS M HAMM
• 金额: $ 35.88万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632685
• 关键词: Adverse effects; Animals; Automobile Driving; Characteristics; Complex; Conditioned Reflex; Contusions; Development; Evaluation; Exercise; Frequencies; Generations; Goals; Individual; Injury; Knowledge; Measures; Modeling; Motor; Motor Activity; Motor Neurons; Movement; Muscle; Muscle Fibers; Muscle Spasticity; Pathway interactions; Patients; Peripheral; Physical therapy exercises; Property; Rattus; Recovery; Reflex action; Research; Residual state; Source; Spinal; Spinal Cord; Spinal Cord Plasticity; Spinal cord injury; Synapses; System; Testing; Training; conditioning; functional restoration; motor deficit; public health relevance; reinnervation; research study; response; response to injury; simulation; synaptic inhibition

Project summary Following spinal cord injury, alterations occur in the properties of spinal motoneurons and in the excitatory and inhibitory synaptic pathways that converge upon them. This plasticity has been considered an adaptive response to injury, compensating for loss of descending drive. Alternatively, such alterations may be maladaptive, contributing to muscle spasticity and coactivation of antagonist muscle groups following injury. The plasticity of the spinal cord also offers the promise of therapies to restore function and ameliorate adverse effects following spinal cord injury through such measures as locomotor training and reflex conditioning. In this project we will identify changes in the organization of motoneuron pools following incomplete spinal cord injuries, the effect of locomotor training on these changes, and the impact of these changes on motoneuron pool function. These studies will be conducted using a rat model of incomplete spinal cord injury in which a spinal cord injury is produced by contusion while the animal is deeply anesthetized. Uninjured rats will be compared to those with incomplete spinal cord injury and to rats with incomplete spinal cord injury given access to voluntary locomotor exercise. These groups of rats will be compared with respect to 1) the strength and distribution in a motoneuron pool of a reflex source and a central (descending and propriospinal) source of synaptic excitation; 2) the strength and distribution of a reflex source of synaptic inhibition; and 3) the contractile properties of muscle fibers innervated by this group of motoneurons. The organization of each of these systems will be characterized according to the intrinsic properties of the motoneurons and their discharge characteristics. The functional impact of changes produced by incomplete spinal cord injury and by exercise therapy following injury will be assessed by simulation, using a dynamic model of an antagonist pair of motoneuron pool-muscles whose parameters incorporate the changes in synaptic, motoneuron pool and muscle organization observed in these studies. The overall goal of this project is to gain an understanding of the effects of a common type of spinal cord injury on the organization and function of a motoneuron pool and the muscle it controls and to assess the benefits and limitations locomotor training.

项目摘要 脊髓损伤后，脊髓运动神经元的特性以及兴奋性和兴奋性神经元的功能发生改变， 抑制性突触通路汇聚在它们上面。这种可塑性被认为是一种适应性 对受伤的反应，补偿下降驱动力的损失。可替代地，这样的改变可以是可替换的。 适应不良，导致肌肉痉挛和损伤后拮抗肌群的共激活。 脊髓的可塑性也提供了恢复功能和改善不良反应的治疗前景。 通过运动训练和反射条件反射等措施对脊髓损伤后的影响。在这 我们将确定脊髓不全后运动神经元池组织的变化 运动训练对这些变化的影响，以及这些变化对运动神经元的影响 池函数这些研究将使用不完全脊髓损伤的大鼠模型进行， 脊髓损伤是在动物深度麻醉时由挫伤产生的。未受伤的老鼠将 与不完全脊髓损伤的大鼠相比， 进行自主运动。将比较这些大鼠组的1）强度 和分布在运动神经元池的反射源和中央（下行和propriospinal）源， 突触兴奋; 2）突触抑制反射源的强度和分布;以及3） 由这组运动神经元支配的肌纤维的收缩特性。每一个组织 这些系统将根据运动神经元的内在特性及其 放电特性不完全性脊髓损伤和脊髓损伤引起的变化对功能的影响 损伤后的运动治疗将通过模拟进行评估，使用拮抗剂对的动力学模型， 运动神经元池-肌肉，其参数包括突触、运动神经元池和 在这些研究中观察到的肌肉组织。本项目的总体目标是了解 一种常见类型的脊髓损伤对运动神经元池的组织和功能的影响， 它控制的肌肉，并评估运动训练的好处和局限性。