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.

项目总结/文摘