Muscle Biological and Biomechanical Response in Cerebral Palsy

描述（由申请人提供）：头部损伤、中风、脊髓损伤和脑瘫（CP）后发生的关节挛缩具有破坏性的功能后果。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，不一定能恢复肌肉功能。本建议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。具体的上运动神经元病变（UMN）的研究人群是脑瘫（CP）儿童。这是由于在康复环境中看到的大量CP儿童以及因挛缩而接受手术矫正的人数（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。这项建议的具体目标是：（1）确定患有CP的儿童的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）确定肌肉和/或结缔组织特性被临床检查准确反映的程度，和（3）测量人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相比的生物学反应。该建议是基于从实际人体肌肉中初步获得的挛缩后由于上运动神经元病变。除了增加我们对挛缩后肌肉的理解外，这些实验可能会导致新的非手术干预来治疗骨骼肌挛缩。

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.