Remote Ischemic Conditioning to Enhance Motor Learning and Corticospinal Excitability in Children with Unilateral Cerebral Palsy

远程缺血调理可增强单侧脑瘫儿童的运动学习和皮质脊髓兴奋性

• 批准号: 10380301
• 负责人: Swati Manoharrao Surkar
• 金额: $ 16.38万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380301
• 关键词: Acute; Affect; Age; Animal Model; Behavior Therapy; Behavioral; Biostatistical Methods; Blood Pressure; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; Cerebral Palsy; Child; Childhood; Classification; Clinical; Clinical Trials; Disease; Dose; Effectiveness; Elderly; Enrollment; Equilibrium; Foundations; Future; Glutamates; Goals; Hand; Human; Impairment; Individual; Intervention; Ischemia; Knowledge; Learning Skill; Leg; Limb structure; Live Birth; Manuals; Methods; Motor; Motor Cortex; Motor Evoked Potentials; Motor Skills; Movement; Myocardium; Nature; Neurobiology; Neuronal Plasticity; Neurons; Organ; Outcome; Performance; Periodicity; Population; Process; Protocols documentation; Quality of life; Randomized Controlled Trials; Recurrence; Rehabilitation Outcome; Rehabilitation therapy; Reperfusion Therapy; Research; Rest; Severities; Side; Speed; Stroke; System; Techniques; Technology; Time; Training; Transcranial magnetic stimulation; Translating; United States; Upper Extremity; Work; acute stroke; angiogenesis; arm; arm function; arm paresis; base; blind; cardioprotection; conditioning; cost; disability; effective intervention; efficacious intervention; functional outcomes; gamma-Aminobutyric Acid; improved; improved functioning; ischemic conditioning; motor learning; motor skill learning; neuroimaging; neuroprotection; neuroregulation; noninvasive brain stimulation; novel; novel strategies; organ injury; phase 2 designs; phase II trial; post intervention; pre-clinical; pressure; rehabilitation strategy; remote delivery; repetitive task practice; skills; skills training; stroke model; young adult

PROJECT SUMMARY/ABSTRACT Unilateral cerebral palsy (UCP) is a leading cause of childhood disability. An early brain injury impairs the upper extremity function, bimanual coordination, and impacts the child's independence. The effectiveness of existing rehabilitation approaches to improve the paretic arm function is limited due to higher training doses, modest effect sizes, and poor retention of training effects. Thus, there is a critical need to find an effective priming agent that, when paired with motor (bimanual) skill training, will facilitate neurobiological processes to enhance the magnitude of training effects and improve functional capabilities of children with UCP. This proposal aims to determine the effects of a novel priming agent, remote ischemic conditioning (RIC), when paired with bimanual skill training to enhance bimanual skill learning and to augment skill dependent plasticity in children with UCP. Ischemic conditioning (IC) is a phenomenon of protecting the target organ from ischemia by directly exposing it to brief episodes of sublethal ischemia. RIC is a clinically feasible way of performing IC where episodes of ischemia and reperfusion are delivered with cyclic inflation and deflation of a blood pressure cuff on the arm or leg. Pre-clinical and preliminary clinical trials in humans show neuroprotective effects of RIC. Our prior work has shown that when paired with motor training, RIC enhances motor learning in healthy individuals. Based on these diversified benefits of RIC, our central hypothesis is that the multifactorial mechanisms of RIC can be harnessed as a priming agent to enhance motor learning and augment neuroplasticity in children with UCP. Our Specific Aims are: 1) to determine the effects of RIC + training on bimanual skill performance, and 2) to determine the effects of RIC + training on corticospinal randomized controlled trial, 30 children with UCP will first upper conditioning excitability undergo bimanual speed stack performance, functional extremity, and Transcranial Magnetic Stimulation assessments. Children will then undergo RIC/Sham plus training. in children with UCP. In this triple blind, We will deliver RIC/sham conditioning via cyclic inflation and deflation of a pressure cuff on the paretic arm using a standard protocol. Training will involve 5 days (15 trials/day) of bimanual speed stack training. Thechildren will perform the same baseline assessmentspost-intervention. We hypothesize that compared to sham conditioning + training, RIC + training will significantly enhance: 1) bimanual skill performance (decrease in movement time (sec) to complete bimanual speed stack task), 2) bimanual function (increase in the Assisting Hand Assessment scores), 3) cortical excitability in the ipsilesional primary motor cortex (M1) (larger amplitude of motor evoked potentials and lower resting or active motor thresholds), and 4) reduce motor cortex inhibition (reduced short-interval intracortical inhibition and increase in intracortical facilitation in ipsilesional M1). Our long-term goal is to develop effective interventions to improve function of children with UCP. Outcomes of this project will provide critical ingredients for designing Phase II trials that will determine the effects of RIC combined with intensive behavioral interventions to improve functional outcomes in children with UCP.

项目摘要/摘要 单侧脑瘫（UCP）是儿童残疾的主要原因。早期脑损伤会损害 上肢功能，双人协调，并影响孩子的独立性。有效性 由于较高的训练剂量，现有的康复方法改善偏度臂功能受到限制 适度的效果大小，培训效果的保留不佳。因此，迫切需要找到有效的启动 当与电动机（双人）技能培训配对时，代理将有助于神经生物学过程 训练效果的幅度并提高UCP儿童的功能能力。该建议旨在 确定新型底漆剂，远程缺血条件（RIC）的影响，与双人 技能培训以增强双人技能学习并增强UCP儿童的技能依赖性可塑性。 缺血性调节（IC）是通过直接保护目标器官免受缺血的现象 将其暴露于余精缺血的简短发作。 RIC是一种在临床上可行的执行IC的方法 缺血和再灌注的发作是通过环状通货膨胀和血压袖带的放气输送的 手臂或腿。人类的临床前和初步临床试验显示RIC的神经保护作用。我们的 先前的工作表明，与运动训练配对时，RIC可以增强健康个体的运动学习。 基于RIC的这些多样化的好处，我们的中心假设是RIC的多因素机制 可以作为启动剂来利用，以增强运动学习和增强儿童的神经塑性 UCP。我们的具体目的是：1）确定RIC +培训对双人技能性能的影响，以及2） 确定RIC +训练对皮质脊髓的影响 随机对照试验，有30名UCP儿童将首先 上 调理 兴奋性 接受双人速度堆栈性能，功能性 肢体和经颅磁刺激评估。然后，孩子们将经历RIC/假 加上培训。 在UCP的孩子中。在这个三重盲人中， 我们将通过循环膨胀和压力放气进行RIC/假条件 使用标准方案在圆臂上袖口。培训将涉及5天（每天15次试验）的双速度速度 堆栈培训。 Thechildren将执行相同的基线评估点干预。我们假设这一点 与假条件 +培训相比，RIC +训练将显着增强：1）双人技能性能 （减少运动时间（SEC）完成双层速度堆栈任务），2）双人功能（增加 辅助手评估得分），3）IPSILESILATIAL AIRPER MOTOR CORTEX（M1）中的皮质兴奋性（较大 电动机诱发电位的振幅和较低的静息或主动电动机阈值），4）减少运动皮层 抑制作用（减少了间体内抑制作用和iPsilesional M1中心脏内促进的增加）。 我们的长期目标是制定有效的干预措施，以改善UCP儿童的功能。结果 该项目将为设计II阶段试验提供关键成分，以确定RIC的影响 结合强化行为干预措施，以改善UCP儿童的功能结果。