Muscle Biological and Biomechanical Response in Cerebral Palsy

描述(申请人提供)：头部损伤、中风、脊髓损伤和脑性瘫痪(CP)后发生的关节痉挛会造成毁灭性的功能后果。肌挛缩是康复过程中的一个令人头疼的障碍，许多时候，唯一的治疗方法是手术移位或松解肌腱，这两种方法都是高度侵入性的，不一定能恢复肌肉功能。这项建议的目的是了解肌肉在肌挛缩形成后发生的变化，并测试保守的治疗方案。要研究的特殊上运动神经元病变(UMN)人群是脑性瘫痪(CP)儿童。这是由于在康复环境中看到了大量患有CP的儿童，以及接受手术矫正肌挛缩(使他们的肌肉组织可用)的人数。术后将对肌挛缩症患者肌肉的生物力学和结构特性进行体外测量，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，以确定激活的生理通路如何解释所获得的功能结果。这项建议的具体目的是：(1)确定CP儿童肌肉的生物和生物力学特性，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)确定肌肉和/或结缔组织特性在临床检查中准确反映的程度；以及(3)测量人类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的生物反应。这一建议是基于从由于上运动神经元损伤而导致的肌肉痉挛后的实际人体肌肉中初步获得的。除了增加我们对肌挛缩症后肌肉的了解外，这些实验还可能导致治疗骨骼肌挛缩症的新的非手术干预措施。 公共卫生相关性：头部损伤、中风、脊髓损伤、多发性硬化症和脑瘫后发生的骨骼肌挛缩是毁灭性的。它们会限制手臂和腿的功能，会妨碍卫生，还会导致极度疼痛。这一应用的目的是研究肌挛缩如何形成，并开发非手术治疗方法。

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.