Respiratory motor control in the intact and injured spinal cord

完整和受损脊髓的呼吸运动控制

• 批准号: 10811209
• 负责人: Tatiana Bezdudnaya
• 金额: $ 40.56万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-11 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10811209
• 关键词: Anatomy; Animals; Behavior; Behavioral; Bilateral; Biological Markers; Breathing; Cervical spinal cord injury; Chronic; Compensation; Data; Electromyography; Electrophysiology (science); Functional disorder; Genetic Recombination; Goals; Histology; Hypercapnia; Hypoxia; Implanted Electrodes; Individual; Injury; Knowledge; Lateral; Methods; Modeling; Motor; Muscle; Musculoskeletal System; Neck; Neural Pathways; Operative Surgical Procedures; Organism; Output; Pattern; Rattus; Recovery; Recovery of Function; Research; Respiration; Respiration Disorders; Respiratory Diaphragm; Respiratory Muscles; Respiratory System; Respiratory physiology; Rest; Series; Severities; Side; Sleep Stages; Slow-Wave Sleep; Source; Spinal; Spinal Cord; Spinal cord injury; System; Time; Vertebral column; Weight; Work; awake; blind; effective therapy; environmental change; experimental study; expiration; improved; independent component analysis; injured; injury recovery; innovation; mathematical analysis; motor control; neural; neural patterning; novel marker; recruit; respiratory; respiratory challenge; response; sham surgery; synergism; timeline; vigilance

Respiratory deficits are a common consequence of cervical spinal cord injury (SCI). This is primarily due to damage to the neural pathways controlling the respiratory muscles, including diaphragm – the primary muscle of respiration. Respiratory activity can spontaneously improve after SCI, however, the extent of recovery is limited and severe respiratory deficits persist. Despite considerable research efforts, the mechanisms of respiratory recovery post-SCI remain unknown. Here, we will use the concept of the modular organization of motor control to study the intact respiratory system and its deficits and recovery in cervical SCI rats. The modular organization of motor control was proposed several decades ago and had been mainly developed with a focus on the locomotor system. In this work, for the first time, we will study the modular organization of respiratory control and its changes after cervical SCI in freely behaving rats. A C2 spinal cord segment hemisection (C2Hx) will be employed as a model of SCI. Electromyograms (EMG) from multiple respiratory muscles will be recorded, and independent component analysis (ICA) will be used to identify a set of modules responsible for controlling different respiratory behaviors. ICA will extract respiratory modules presented by neural patterns (drive primitives) that activate groups of respiratory muscles with different weights, called synergies. Breathing is very heterogeneous and can be divided into many types, including resting and active breathing, challenged breathing, and breathing during different stages of sleep. We hypothesize that different types of breathing are organized by combining different modules. Therefore, the goals of the proposed work are to 1) identify those basic respiratory modules and their arrangements to produce various respiratory behaviors in intact rats; 2) evaluate modular changes after cervical SCI; 3) correlate remaining modules immediately after SCI with the extent of spontaneous recovery and lasting respiratory deficits. Overall, this highly innovative study will increase our basic knowledge about the organization of a healthy respiratory system during different behaviors, its deficits, and recovery after cervical SCI and help develop electrophysiological biomarkers to predict the extent of respiratory recovery post-injury.

呼吸缺陷是宫颈脊髓损伤（SCI）的普遍结果。这主要是由于 损害控制呼吸肌的神经途径，包括隔膜 - 主要肌肉 呼吸。 SCI之后，呼吸活动可以自助性地改善，但是，恢复的程度是 有限和严重的呼吸缺陷持续存在。尽管进行了大量的研究工作，但 SCI之后的呼吸恢复仍然未知。在这里，我们将使用模块化组织的概念 运动控制以研究完整的呼吸系统及其在宫颈科学大鼠中的防御性和恢复性。 几十年前提出了模块化组织控制的模块化组织，主要是 开发着专注于运动系统。在这项工作中，我们将第一次研究模块化 在自由表现大鼠的宫颈SCI后的呼吸控制及其变化。 C2脊髓 段半分（C2HX）将作为SCI模型进行。来自多个的肌电图（EMG） 将记录呼吸道肌肉，并将使用独立组件分析（ICA）来确定一组 负责控制不同呼吸行为的模块。 ICA将提取提出的呼吸模块 通过神经模式（驱动原语）激活不同权重的呼吸道肌肉组，称为 协同作用。呼吸非常异构，可以分为多种类型，包括休息和活跃 在不同的睡眠阶段，呼吸，挑战呼吸和呼吸。我们假设这是不同的 通过组合不同的模块来组织呼吸的类型。因此，拟议工作的目标是 到1）确定那些基本的呼吸模块及其产生各种呼吸行为的安排 在完整的大鼠中； 2）评估宫颈科学后的模块化变化； 3）紧随其后的剩余模块 SCI具有赞助恢复和持久的呼吸缺陷程度。 总体而言，这项高度创新的研究将增加我们对健康组织的基本知识 在不同行为时，呼吸系统在宫颈SCI后定义和恢复，并有助于发展 电生理生物标志物可预测伤害后呼吸道恢复的程度。