Origins of Increased Motoneuron Excitability in Hemispheric Stroke

半球中风运动神经元兴奋性增加的起源

基本信息

批准号：
9926904
负责人：
WILLIAM Zev RYMER
金额：
$ 31.75万
依托单位：
REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-08 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9926904
关键词：
Address Affect Brain Stem Calcium Cell Nucleus Characteristics Clinical Complication Contracture Contralateral Coupled Cutaneous Data Deformity Diagnosis Disease Ear Electric Stimulation Electrophysiology (science)Excitatory Postsynaptic Potentials Exhibits Eye Fiber Flexor Forearm Functional disorder H-Reflex Human Hyperreflexia Isometric Exercise Joints Lead Left Length Limb structure Measures Membrane Methodology Motion Motor Motor Neurons Movement Muscle Muscle Hypertonia Muscle Spasticity Muscle Tonus Neck Neurons Norepinephrine Nuclear Phase Physiological Population Probability Property Records Recovery Reflex action Resistance Rest Sampling Serotonin Side Sodium Source Spinal Spinal Cord Stimulus Stretching Stroke Surface Survivors Synapses Synaptic Potentials System Techniques Technology Tendon structure Time Treatment outcome base biceps brachii muscle design falls hemiparetic stroke median nerve monoamine neurophysiology new technology novel novel therapeutic intervention personalized diagnostics public health relevance receptor recruit response reticulospinal tract sound spasticity spinal pathway stretch reflex stroke survivor tool vestibular pathway voltage

项目摘要

DESCRIPTION (provided by applicant): Spasticity is a common complication of hemispheric stroke, impacting 40% or more of stroke survivors. Its most visible clinical feature is muscular hypertonia, or increased resistance of a limb to externally imposed motion. If left untreated, this increase in tone can impede joint motion, limiting recovery of voluntary movement. In addition, spasticity may lead to persistent muscle shortening, giving rise to joint deformity, and to muscle contracture. The pathophysiology appears to depend on an enhancement of the stretch reflex response, but we do not know where this enhancement originates. Accordingly, this proposal seeks to explore the physiological origins of spastic hypertonia by examining several alternative hypotheses about the basic underlying mechanisms. First, there could be greater excitatory synaptic drive to the spinal motoneuron pool, arising from key descending spinal pathways such as the vestibulospinal and/or reticulospinal tracts. Second, there could be larger, and/or longer-duration Ia excitatory synaptic potentials (EPSP'S) in spinal motoneurons elicited by the muscle stretch. Third, there could be changes in the intrinsic membrane properties of motoneurons such as in voltage-gated conductances of motoneurons, giving rise to persistent inward currents, or "PIC's". We plan to explore these mechanisms in hemispheric stroke survivors, using advanced EMG recording technologies, coupled with the use of a novel tendon probe (the Linmot), which imposes controlled muscle length changes on the muscle (the biceps muscle) and records biceps muscle force. These approaches, when combined, should allow us to separate the relative contributions of the proposed mechanisms, and should help us to develop greater diagnostic precision about the physiological characteristics of spasticity, as well as to design novel therapeutic approaches.

描述（由申请人提供）：痉挛是半球中风的常见并发症，影响 40% 或更多的中风幸存者，其最明显的临床特征是肌肉张力过高，或者肢体对外部施加的运动的抵抗力增加，如果不及时治疗，就会出现这种情况。张力的增加会阻碍关节运动，限制随意运动的恢复。此外，痉挛可能导致持续的肌肉缩短，导致关节畸形和肌肉挛缩。病理生理学似乎取决于牵张反射反应的增强。但我们不知道这种增强的起源。因此，该提议旨在通过检查有关基本潜在机制的几种替代假设来探索痉挛性张力亢进的生理学起源。第二，肌肉拉伸引起的脊髓运动神经元中可能存在更大和/或持续时间更长的 Ia 兴奋性突触电位（EPSP'S）。运动神经元的内在膜特性可能会发生变化，例如运动神经元的电压门控电导，从而引起持续的内向性我们计划使用先进的肌电图记录技术，并结合使用新型肌腱探针（Linmot）来探索半球中风幸存者的这些机制，该探针对肌肉（二头肌）施加受控的肌肉长度变化。肌肉）并记录二头肌力量。这些方法结合起来，应该能让我们区分所提出的机制的相对贡献，并有助于我们对痉挛的生理特征进行更高的诊断精度，并设计新的治疗方法。接近。