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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/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、双手协调性，影响孩子的独立性。的有效性由于训练剂量较高，现有的改善瘫痪手臂功能的康复方法受到限制，效果大小适中，训练效果的保留性较差。因此，迫切需要找到一种有效的启动方法当与运动（双手）技能训练相结合时，将促进神经生物学过程以增强训练效果的大小和 UCP 儿童功能能力的提高。该提案旨在确定新型启动剂、远程缺血调节 (RIC) 与双手配合使用时的效果技能培训，以增强 UCP 儿童的双手技能学习和增强技能依赖性可塑性。缺血调节（IC）是通过直接保护靶器官免受缺血的现象使其暴露于短暂的亚致死性缺血。 RIC 是一种临床上可行的 IC 方法，其中缺血和再灌注的发生是通过血压袖带的循环充气和放气来实现的。手臂或腿。人体临床前和初步临床试验显示 RIC 具有神经保护作用。我们的先前的研究表明，当与运动训练相结合时，RIC 可以增强健康个体的运动学习。基于 RIC 的这些多样化益处，我们的中心假设是 RIC 的多因素机制可以用作启动剂来增强患有以下疾病的儿童的运动学习和神经可塑性 UCP。我们的具体目标是：1) 确定 RIC + 训练对双手技能表现的影响，以及 2) 确定 RIC + 训练对皮质脊髓的影响随机对照试验，首先对 30 名 UCP 儿童进行上调理兴奋性经过双手速叠性能、功能四肢和经颅磁刺激评估。然后孩子们将接受 RIC/Sham 再加上培训。患有 UCP 的儿童。在这场三盲赛中，我们将通过压力的循环膨胀和通货紧缩来提供 RIC/假调节使用标准方案将袖带戴在瘫痪手臂上。训练将涉及 5 天（每天 15 次试验）的双手速度堆栈训练。孩子们将在干预后进行相同的基线评估。我们假设与假调节+训练相比，RIC+训练将显着增强：1）双手技能表现（减少完成双手速度堆栈任务的移动时间（秒）），2）双手功能（增加辅助手评估分数），3）同病初级运动皮层（M1）（较大运动诱发电位的幅度和较低的静息或活动运动阈值），以及 4）减少运动皮层抑制（同病灶 M1 中短间隔皮质内抑制减少，皮质内促进增加）。我们的长期目标是开发有效的干预措施来改善 UCP 儿童的功能。结果该项目将为设计 II 期试验提供关键要素，以确定 RIC 的效果结合强化行为干预来改善 UCP 儿童的功能结果。