Breathing Research and Therapeutics Center, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Exp Neurol. 2021 Aug;342:113751. doi: 10.1016/j.expneurol.2021.113751. Epub 2021 May 8.
Impaired respiratory function is a common and devastating consequence of cervical spinal cord injury. Accordingly, the development of safe and effective treatments to restore breathing function is critical. Acute intermittent hypoxia has emerged as a promising therapeutic strategy to treat respiratory insufficiency in individuals with spinal cord injury. Since the original report by Bach and Mitchell (1996) concerning long-term facilitation of phrenic motor output elicited by brief, episodic exposure to reduced oxygen, a series of studies in animal models have led to the realization that acute intermittent hypoxia may have tremendous potential for inducing neuroplasticity and functional recovery in the injured spinal cord. Advances in our understanding of the neurobiology of acute intermittent hypoxia have prompted us to begin to explore its effects in human clinical studies. Here, we review the basic neurobiology of the control of breathing and the pathophysiology and respiratory consequences of two common experimental models of incomplete cervical spinal cord injury (i.e., high cervical hemisection and mid-cervical contusion). We then discuss the impact of acute intermittent hypoxia on respiratory motor function in these models: work that has laid the foundation for translation of this promising therapeutic strategy to clinical populations. Lastly, we examine the limitations of these animal models and intermittent hypoxia and discuss how future work in animal models may further advance the translation and therapeutic efficacy of this treatment.
呼吸功能障碍是颈椎脊髓损伤的常见且严重的后果。因此，开发安全有效的治疗方法来恢复呼吸功能至关重要。急性间歇性低氧已成为治疗脊髓损伤患者呼吸功能不全的一种有前途的治疗策略。自 Bach 和 Mitchell（1996 年）关于通过短暂、间歇性的低氧暴露引起膈神经运动输出的长期易化的原始报告以来，一系列动物模型研究使人们认识到，急性间歇性低氧可能在诱导损伤脊髓的神经可塑性和功能恢复方面具有巨大的潜力。我们对急性间歇性低氧神经生物学的理解的进步促使我们开始探索其在人类临床研究中的作用。在这里，我们回顾了呼吸控制的基本神经生物学以及两种常见的不完全颈脊髓损伤实验模型（即高位颈半切和中颈挫伤）的病理生理学和呼吸后果。然后，我们讨论了急性间歇性低氧对这些模型中呼吸运动功能的影响：这项工作为将这一有前途的治疗策略转化为临床人群奠定了基础。最后，我们检查了这些动物模型和间歇性低氧的局限性，并讨论了动物模型中的未来工作如何进一步提高这种治疗方法的转化和治疗效果。
