Locke Katherine C, Randelman Margo L, Hoh Daniel J, Zholudeva Lyandysha V, Lane Michael A
Department of Neurobiology & Anatomy, Drexel University; Marion Murray Spinal Cord Research Center, Philadelphia, PA, USA.
Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Neural Regen Res. 2022 Oct;17(10):2141-2148. doi: 10.4103/1673-5374.335839.
The study of respiratory plasticity in animal models spans decades. At the bench, researchers use an array of techniques aimed at harnessing the power of plasticity within the central nervous system to restore respiration following spinal cord injury. This field of research is highly clinically relevant. People living with cervical spinal cord injury at or above the level of the phrenic motoneuron pool at spinal levels C3-C5 typically have significant impairments in breathing which may require assisted ventilation. Those who are ventilator dependent are at an increased risk of ventilator-associated co-morbidities and have a drastically reduced life expectancy. Pre-clinical research examining respiratory plasticity in animal models has laid the groundwork for clinical trials. Despite how widely researched this injury is in animal models, relatively few treatments have broken through the preclinical barrier. The three goals of this present review are to define plasticity as it pertains to respiratory function post-spinal cord injury, discuss plasticity models of spinal cord injury used in research, and explore the shift from preclinical to clinical research. By investigating current targets of respiratory plasticity research, we hope to illuminate preclinical work that can influence future clinical investigations and the advancement of treatments for spinal cord injury.
在动物模型中对呼吸可塑性的研究跨越了数十年。在实验台上,研究人员使用一系列技术,旨在利用中枢神经系统内的可塑性力量,在脊髓损伤后恢复呼吸功能。这一研究领域具有高度的临床相关性。在脊髓C3 - C5节段膈运动神经元池水平或以上发生颈脊髓损伤的患者,通常在呼吸方面有显著障碍,可能需要辅助通气。那些依赖呼吸机的患者发生呼吸机相关合并症的风险增加,预期寿命大幅缩短。在动物模型中研究呼吸可塑性的临床前研究为临床试验奠定了基础。尽管在动物模型中对这种损伤的研究非常广泛,但相对较少的治疗方法突破了临床前障碍。本综述的三个目标是定义与脊髓损伤后呼吸功能相关的可塑性,讨论研究中使用的脊髓损伤可塑性模型,并探讨从临床前研究到临床研究的转变。通过研究呼吸可塑性研究的当前靶点,我们希望阐明能够影响未来临床研究和脊髓损伤治疗进展的临床前工作。