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.

呼吸功能障碍是颈脊髓损伤（SCI）的常见后果。这主要是由于 损害控制呼吸肌的神经通路，包括隔膜-主要肌肉 呼吸。呼吸活动在SCI后可以自发改善，然而，恢复的程度是 有限和严重的呼吸功能障碍持续存在。尽管进行了大量的研究工作， 脊髓损伤后呼吸恢复情况尚不清楚。在这里，我们将使用模块化组织的概念， 运动控制，以研究颈脊髓损伤大鼠的完整呼吸系统及其缺陷和恢复。 电机控制的模块化组织是在几十年前提出的，主要是 重点是运动系统在这项工作中，我们将首次研究模块化 自由活动大鼠呼吸控制的组织结构及其在颈脊髓损伤后的变化A C2脊髓 脊髓半切术（C2 Hx）将被用作SCI模型。肌电图（EMG）来自多个 将记录呼吸肌，并使用独立成分分析（伊卡）来识别一组 负责控制不同呼吸行为的模块。伊卡将提取呼吸模块 通过神经模式（驱动原语）激活具有不同权重的呼吸肌群，称为 协同作用。呼吸是非常异质的，可以分为许多类型，包括休息和活动 呼吸，挑战性呼吸，以及不同睡眠阶段的呼吸。我们假设不同的 通过组合不同的模块来组织呼吸类型。因此，拟议工作的目标是 1）识别那些基本的呼吸模块及其排列以产生各种呼吸行为 在完整大鼠中; 2）评估颈脊髓损伤后的模块变化; 3）在脊髓损伤后立即将剩余模块 SCI的自发恢复程度和持续的呼吸功能障碍。 总的来说，这项高度创新的研究将增加我们对健康组织的基本知识。 呼吸系统在不同的行为，其赤字和恢复后，颈椎脊髓损伤，并帮助发展 电生理学生物标志物来预测损伤后呼吸恢复的程度。