Stimulation of novel spinal respiratory circuit to restore breathing in ventilator-dependent patients with SCI.

刺激新型脊髓呼吸回路以恢复依赖呼吸机的 SCI 患者的呼吸。

• 批准号: 10112480
• 负责人: Daniel Lu
• 金额: $ 127.78万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10112480
• 关键词: Acute; Air; Algorithms; Area; Behavior; Behavioral; Brain Stem; Breathing; Cause of Death; Cervical; Cervical spinal cord injury; Cervical spine; Cessation of life; Chronic; Clinical; Communication; Complex; Dangerousness; Data; Dorsal; Dose; Electric Stimulation; Electrodes; Electrophysiology (science); Enrollment; Goals; Hand; Impaired health; Implant; Lead; Location; Lung; Mechanical ventilation; Mechanics; Morbidity - disease rate; Motor output; Muscle function; Neurologic; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Output; Pain; Pathway interactions; Patients; Pattern; Physiological; Pump; Quality of life; Recovery; Recovery of Function; Rehabilitation therapy; Research; Residual state; Respiration; Respiratory Failure; Respiratory Muscles; Respiratory physiology; Risk; Sensory; Site; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; System; Testing; Therapeutic; Thinking; Training; Upper Extremity; Ventilator; Vertebral column; Volition; Weaning; cost; density; early phase clinical trial; functional gain; high risk; improved; injured; millisecond; mortality; muscle strength; nervous system disorder; neural circuit; neural network; neuromechanism; neuroregulation; novel; partial response; respiratory; response; restoration; safety and feasibility; ventilation

PROJECT SUMMARY/ABSTRACT Respiratory failure after spinal cord injury (SCI) impairs the health of the injured patients, and respiratory failure is the leading cause of death in patients with SCI. Treatment of respiratory failure consists of mechanical ventilation, in which a mechanical pump is used to facilitate air exchange with the lungs. Mechanical ventilation is invasive, costly, limiting, and carries with it a high risk of complications and death. Mechanical ventilation provides an unvarying pattern of ventilation that is not responsive to physiological demands; it does not recapitulate normal breathing. Normal breathing is a complex behavior under both voluntary and involuntary neural control; it is responsive (in milliseconds or less) to the physiological state of the patient. Restoration of fully integrated, naturalistic breathing would represent a significant advance in the treatment of respiratory failure following SCI. The main hurdle to accessing the neural network for breathing for therapeutic purposes is that the neural mechanisms controlling respiration reside deep in the brainstem, which is dangerous to access surgically. Recently, we elucidated a novel breathing pathway in the spinal cord that can be modulated by electrical stimulation of the cervical spine, an area that is surgically accessible. We have compiled significant data that stimulating the cervical spine can restore or augment breathing. Clinically approved epidural spinal cord stimulators exist to treat pain, and these stimulators can also be used to stimulate the cervical spine to restore respiratory function. The main objective of this project is to provide proof of the concept that cervical epidural stimulation can improve respiratory function in ventilator-dependent patients with SCI and define the stimulation parameters that most effectively restore more normal breathing. The deliverables for this 5-year project include establishing the safety and feasibility of epidural stimulation for respiratory rehabilitation in SCI and providing an algorithm to select the optimum stimulation variables to augment respiratory activity in each patient (e.g., stimulation site, dose, and timing). If successful, we anticipate using epidural stimulation to partially or completely wean each patient with SCI off mechanical ventilation, which would have immediate benefits — increased independence, improved quality of life, and decreased costs and risks associated with mechanical ventilation. Conventional thinking is that once the spinal cord is injured, little or no functional recovery is possible. This dire sense of irrreversibility is at odds with our research in spinal cord neuromodulation, which has shown that substantial recovery of voluntary hand and upper extremity function can result from epidural spinal cord stimulation. A similar neurmodulatory strategy may be used to augment or restore respiratory function in patients with SCI. If successful, this neuromodulatory strategy to restore respiratory function may usher in a new era of respiratory neurorehabiltitation for SCI, and potentially other neurological disorders, and transform our understanding of neural circuits governing respiration and the plasticity of injured states of the spine.

项目摘要/摘要 脊髓损伤后的呼吸衰竭（SCI）会损害受伤患者的健康，呼吸衰竭 是SCI患者死亡的主要原因。呼吸衰竭的治疗包括机械 通风，其中使用机械泵来促进与肺部的空气交换。机械通气 具有侵入性，昂贵，限制，并带有并发症和死亡的高风险。机械通气 提供了一种不变的通风模式，该模式对身体需求不反应；它没有 概括正常呼吸。在自愿和非自愿下，正常呼吸是一种复杂的行为 神经控制；它对患者的身体状态的反应灵敏（以毫秒或更少）。修复 完全整合，自然主义的呼吸将代表呼吸衰竭的重大进展 跟随科学。访问神经网络以进行治疗目的的主要障碍是 控制呼吸的神经机制位于脑干深处，这是危险的手术。 最近，我们在脊髓中阐明了一种新型的呼吸途径，可以通过电气调节 刺激颈椎，该区域是可以手术访问的区域。我们编制了重要的数据 刺激颈椎可以恢复或增加呼吸。临床认可的硬膜外脊髓 存在刺激剂来治疗疼痛，这些刺激剂也可用于刺激颈椎恢复 呼吸功能。该项目的主要目的是提供颈椎硬膜外概念的证明 刺激可以改善依赖SCI的呼吸机依赖性患者的呼吸功能，并定义刺激 最有效地恢复更正常呼吸的参数。这个5年项目的可交付成果包括 建立硬膜外刺激对SCI呼吸康复的安全性和可行性，并提供 算法选择最佳刺激变量以增加每个患者的呼吸活动（例如， 刺激部位，剂量和时机）。如果成功，我们预计会使用硬膜外刺激部分或完全 断奶的每个患者具有SCI的机械通气，这将有直接的好处 - 增加 独立性，改善生活质量以及与机械通气相关的成本和风险改善。 常规思维是，一旦脊髓受伤，几乎没有功能恢复。这个可怕的 不可逆性的感觉与我们在脊髓神经调节中的研究不符，这表明 硬膜外脊髓可以实质性地恢复自愿手和上肢功能 刺激。类似的神经调节策略可用于增强患者的呼吸功能 与科幻。如果成功，这种恢复呼吸功能的神经调节策略可能会引入一个新时代 SCI以及可能其他神经系统疾病的呼吸神经疗法，并改变我们 了解呼吸的神经回路和脊柱受伤状态的可塑性。