Novel Actions of Acute Intermittent Hypoxia in Hemispheric Stroke

半球脑卒中急性间歇性缺氧的新作用

• 批准号: 10575870
• 负责人: WILLIAM Zev RYMER
• 金额: $ 45.38万
• 依托单位: REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10575870
• 关键词: Acute; Adoption; Air; Animal Model; Automobile Driving; Brain; Brain Stem; Brain-Derived Neurotrophic Factor; Breathing; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cerebrovascular Disorders; Cerebrum; Cervical spinal cord structure; Chronic; Clinical; Contralateral; Data; Development; Distal; Economic Burden; Elbow; Ensure; Event; Exposure to; Extensor; Flexor; Fostering; Gases; Hand; Human; Hypoxia; Impairment; Institution; Intervention; Investigation; Ischemic Stroke; Limb structure; Link; Measurement; Modality; Motor; Muscle; Muscle Spasticity; Neuraxis; Neuronal Plasticity; Oxygen; Paresis; Pathology; Pathway interactions; Patients; Persons; Population; Probability; Proteins; Protocols documentation; Public Health; Recovery; Recovery of Function; Reflex action; Research; Research Personnel; Research Project Grants; Residual state; Respiratory physiology; Risk; Sensory; Serotonergic System; Severities; Spatial Distribution; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Stroke; Surface; Synaptic Transmission; Techniques; Technology; Therapeutic; Translational Research; Traumatic injury; Treatment Protocols; United States; United States National Institutes of Health; Universities; Upper Extremity; Work; adverse outcome; cerebrovascular; clinical application; density; dexterity; disability; multidisciplinary; muscle strength; novel; novel therapeutic intervention; novel therapeutics; participant safety; programs; recruit; respiratory; response; restoration; restorative treatment; safety study; serotonin receptor; spasticity; spinal tract; stroke patient; stroke survivor; stroke therapy; white matter

PROJECT SUMMARY/ABSTRACT Stroke is the second leading cause of death and a leading cause of long-term disability worldwide. Despite the spontaneous recovery that occurs following a hemispheric stroke, more than half of stroke patients have substantial residual impairments, imposing a significant human and economic burden. The objective of this proposal is to investigate the potential of a novel therapeutic intervention — Acute Intermittent Hypoxia (AIH). This technique has shown significant promise in persons with spinal cord injury (SCI) and in our preliminary studies on stroke. AIH constitutes a brief, rapid reduction in oxygen concentration which stimulates the serotonergic pathways of the brainstem, and enhances activity of serotonin receptors in the brain and spinal cord. This results in increased synthesis of a key protein called brain-derived neurotrophic factor (BDNF), potentiating synaptic transmission and driving plasticity in the CNS. In persons with SCI, AIH has been demonstrated to be safe and cause broad-ranging changes in the CNS, including transient improvements in respiratory function, locomotor function, and hand dexterity. In this proposal we will extend our promising research on AIH-initiated plasticity in SCI patients to persons with stroke. Our specific aims are to (1) To assess the limb segmental distribution of AIH-induced increases in muscle activation in paretic limbs of stroke survivors, comparing strength measurements taken before and after an AIH sequence; (2) To determine whether AIH increases the severity of spasticity using reflex threshold measurements in spastic muscles. Here, we plan to use a linear motor (LinMot USA Inc.) to estimate reflex threshold in elbow flexors before and after AIH administration; (3) To evaluate the spatial distribution of motor unit activation in limb muscles using surface EMG grids and to implement motor unit decomposition protocols to determine which types of motor unit are activated following AIH administration. In the short-term, this study will help us gain a greater understanding of the efficacy and underlying mechanism of AIH-induced plasticity in stroke. In the long-term, this research will help establish AIH as both a novel therapeutic modality in and of itself for the treatment of stroke, and also as an adjunct technique to be combined with other intervention techniques. This translational proposal exemplifies the NIH Exploratory/Developmental Research Grant Program (R21) as it fosters developmental research for an emerging intervention that has the potential for several unique clinical applications.

项目概要/摘要 尽管中风是全球第二大死亡原因，也是导致长期残疾的主要原因。 半球中风后发生的自然恢复，超过一半的中风患者 严重的残余损伤，造成重大的人力和经济负担。 该提案的目的是研究一种新型治疗干预措施的潜力——急性 该技术在脊髓损伤（SCI）患者中显示出显着的前景。 在我们对中风的初步研究中，AIH 会导致氧气浓度短暂、快速降低。 刺激脑干的血清素通路，增强大脑中血清素受体的活性 这导致一种称为脑源性神经营养因子的关键蛋白质的合成增加。 (BDNF)，增强中枢神经系统的突触传递并驱动可塑性，在 SCI 患者中，AIH 已被证实。 被证明是安全的，并会引起中枢神经系统的广泛变化，包括短暂的改善 呼吸功能、运动功能和手的灵活性。 在这项提案中，我们将把关于 AIH 引发的 SCI 患者可塑性的有前途的研究扩展到患有以下疾病的人： 我们的具体目标是 (1) 评估 AIH 引起的肌肉增加的肢体节段分布。 中风幸存者偏瘫肢体的激活，比较 AIH 前后进行的力量测量 (2) 使用反射阈值确定 AIH 是否会增加痉挛的严重程度 在这里，我们计划使用线性电机（LinMot USA Inc.）来估计反射。 AIH给药前后肘屈肌的阈值；（3）评估运动的空间分布； 使用表面肌电图网格激活肢体肌肉并实施运动单元分解协议 确定 AIH 给药后哪些类型的运动单位被激活。 从短期来看，这项研究将帮助我们更好地了解其功效和潜在机制 从长远来看，这项研究将有助于将 AIH 确立为一种新型药物。 治疗方式本身用于治疗中风，也可作为一种辅助技术相结合 该转化提案体现了 NIH 探索性/发展性技术。 研究补助金计划（R21），因为它促进新兴干预措施的发展研究，该干预措施具有 具有多种独特临床应用的潜力。