Muscle Biological and Biomechanical Response in Cerebral Palsy

脑瘫的肌肉生物和生物力学反应

• 批准号: 7892163
• 负责人: Richard L. Lieber
• 金额: $ 34.76万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7892163
• 关键词: Affect; Atrophic; Baclofen; Biological; Biomechanics; Cerebral Palsy; Child; Clinical; Complication; Connective Tissue; Contracture; Craniocerebral Trauma; Data; Deafferentation procedure; Development; Disease; Electric Stimulation; Functional disorder; Gene Expression Profile; Genes; Head; Human; Hygiene; Immobilization; In Vitro; Injection of therapeutic agent; Intervention; Intramuscular; Joints; Lead; Leg; Lesion; Measures; Mechanics; Medical; Methods; Modeling; Motor Neurons; Multiple Sclerosis; Muscle; Muscle function; Nature; Nervous system structure; Neurotoxins; Normal tissue morphology; Operative Surgical Procedures; Oral; Orthopedics; Pain; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Physiological; Physiology; Population; Process; Property; Pump; Range of motion exercise; Rehabilitation therapy; Scientist; Signal Transduction; Skeletal Muscle; Spinal cord injury; State of Zero Gravity; Stroke; Surgeon; Syndrome; Tendon Transfer; Testing; Time; Tissues; arm; base; clinical practice; instrument; muscle aging; neurophysiology; novel; prevent; public health relevance; research study; response

DESCRIPTION (provided by applicant): Joint contractures that occur after head injury, stroke, spinal cord injury and cerebral palsy (CP) have devastating functional consequences. Contractures represent a vexing obstacle to the rehabilitation process and many times the only treatment for contracture is surgical tendon transfer or release, both of which are highly invasive and do not necessarily restore muscle function. The purpose of this proposal is to understand the changes that occur in muscles after contracture formation and to test conservative treatment options. The specific upper motor neuron lesion (UMN) population to be studied is children with cerebral palsy (CP). This is due to the large number of children with CP seen in the rehabilitation setting and the number who undergo surgical correction for contracture (making their muscle tissue available). Biomechanical and structural properties of muscle from patients with contractures will be measured in vitro after surgery to determine the basis for the changes in passive mechanical properties. Then, a complete gene expression profile will be generated on these tissues to determine how the physiological pathways activated explain the functional results obtained. The specific aims of this proposal are: (1) to define the biological and biomechanical properties of muscles from children with CP and to contrast and compare these properties with age- and muscle-matched normal tissue, age- and muscle- matched atrophic tissue, (2) To determine the extent to which muscle and/or connective tissue properties are accurately reflected by the clinical exam, and (3) To measure the biological response of human semitendinosus muscles compared to age- and muscle-matched normal tissue, and age- and muscle-matched atrophied tissue. This proposal is based on preliminary obtained from actual human muscles after contracture due to upper motor neuron lesion. In addition to increasing our understanding of muscle after contracture, these experiments may lead to novel, nonsurgical interventions to treat skeletal muscle contractures. PUBLIC HEALTH RELEVANCE: Skeletal muscle contractures that occur after head injury, stroke, spinal cord injury, multiple sclerosis and cerebral palsy are devastating. They limit function of the arms and legs, can prevent hygiene and can cause extreme pain. The purpose of this application is to study how contractures form and to develop nonsurgical methods to treat them.

描述（由申请人提供）：头部受伤、中风、脊髓损伤和脑瘫（CP）后发生的关节挛缩会造成破坏性的功能后果。挛缩是康复过程中的一个令人烦恼的障碍，很多时候，挛缩的唯一治疗方法是手术肌腱转移或松解，这两种方法都是高度侵入性的，并且不一定能恢复肌肉功能。该提案的目的是了解挛缩形成后肌肉发生的变化并测试保守治疗方案。要研究的特定上运动神经元病变（UMN）人群是脑瘫（CP）儿童。这是因为在康复机构中发现了大量患有脑瘫的儿童，并且有大量儿童接受了挛缩手术矫正（使他们的肌肉组织可用）。手术后将在体外测量挛缩患者肌肉的生物力学和结构特性，以确定被动力学特性变化的基础。然后，将在这些组织上生成完整的基因表达谱，以确定激活的生理途径如何解释所获得的功能结果。该提案的具体目标是：(1) 定义 CP 儿童肌肉的生物学和生物力学特性，并将这些特性与年龄和肌肉匹配的正常组织、年龄和肌肉匹配的萎缩组织进行对比和比较，(2) 确定临床检查准确反映肌肉和/或结缔组织特性的程度，以及 (3) 测量人类的生物反应 半腱肌与年龄和肌肉匹配的正常组织以及年龄和肌肉匹配的萎缩组织进行比较。该提议是基于从由于上运动神经元损伤导致挛缩后的实际人体肌肉中获得的初步结果。除了增加我们对挛缩后肌肉的了解之外，这些实验还可能导致治疗骨骼肌挛缩的新颖的非手术干预措施。 公共卫生相关性：头部受伤、中风、脊髓损伤、多发性硬化症和脑瘫后发生的骨骼肌挛缩具有毁灭性。它们限制手臂和腿部的功能，不利于卫生，并可能导致极度疼痛。该应用的目的是研究挛缩是如何形成的并开发非手术方法来治疗它们。