Department of Neurobiology and Anatomy, College of Medicine, Drexel University, 2900 W Queen Lane, Philadelphia, PA 19129, USA.
Department of Neurobiology and Anatomy, College of Medicine, Drexel University, 2900 W Queen Lane, Philadelphia, PA 19129, USA.
Exp Neurol. 2018 Jul;305:56-65. doi: 10.1016/j.expneurol.2018.03.014. Epub 2018 Mar 26.
Unilateral cervical C2 hemisection (C2Hx) is a classic model of spinal cord injury (SCI) for studying respiratory dysfunction and plasticity. However, most previous studies were performed under anesthesia, which significantly alters respiratory network. Therefore, the goal of this work was to assess spontaneous diaphragm recovery post-C2Hx in awake, freely behaving animals. Adult rats were chronically implanted with diaphragm EMG electrodes and recorded during 8 weeks post-C2Hx. Our results reveal that ipsilateral diaphragm activity partially recovers within days post-injury and reaches pre-injury amplitude in a few weeks. However, the full extent of spontaneous ipsilateral recovery is significantly attenuated by anesthesia (ketamine/xylazine, isoflurane, and urethane). This suggests that the observed recovery may be attributed in part to activation of NMDA receptors which are suppressed by anesthesia. Despite spontaneous recovery in awake animals, ipsilateral hemidiaphragm dysfunction still persists: i) Inspiratory bursts during basal (slow) breathing exhibit an altered pattern, ii) the amplitude of sighs - or augmented breaths - is significantly decreased, and iii) the injured hemidiaphragm exhibits spontaneous events of hyperexcitation. The results from this study offer an under-appreciated insight into spontaneous diaphragm activity and recovery following high cervical spinal cord injury in awake animals.
单侧颈 2 半切（C2Hx）是一种经典的脊髓损伤（SCI）模型，用于研究呼吸功能障碍和可塑性。然而，大多数先前的研究都是在麻醉下进行的，这会显著改变呼吸网络。因此，本研究的目的是在清醒、自由活动的动物中评估 C2Hx 后膈神经的自发恢复情况。成年大鼠接受慢性膈神经肌电图电极植入，并在 C2Hx 后 8 周内进行记录。我们的结果表明，损伤后数天内同侧膈神经活动部分恢复，并在数周内恢复到损伤前的幅度。然而，麻醉（氯胺酮/甲苯噻嗪、异氟烷和氨基甲酸乙酯）显著减弱了自发的同侧恢复的程度。这表明观察到的恢复可能部分归因于 NMDA 受体的激活，而麻醉会抑制 NMDA 受体的激活。尽管在清醒动物中存在自发恢复，但同侧膈神经功能障碍仍然存在：i）基础呼吸（慢呼吸）时吸气爆发呈现出改变的模式，ii）叹息或增强呼吸的幅度显著降低，以及 iii）受伤的膈神经会出现自发性的过度兴奋事件。本研究的结果提供了对清醒动物高位颈脊髓损伤后膈神经自发活动和恢复的一种被低估的认识。
