Bezdudnaya Tatiana, Marchenko Vitaliy, Zholudeva Lyandysha V, Spruance Victoria M, Lane Michael A
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. 2017 Jul;293:181-189. doi: 10.1016/j.expneurol.2017.04.003. Epub 2017 Apr 19.
Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm - a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks. Although many studies have shown such plasticity at the level of the spinal cord, much less is known about the changes occurring at supraspinal levels post-SCI. The goal of this study was to determine functional reorganization of respiratory neurons in the medulla acutely (>4h) following high cervical SCI. Experiments were conducted in decerebrate, unanesthetized, vagus intact and artificially ventilated rats. In this preparation, spontaneous recovery of ipsilateral phrenic nerve activity was observed within 4 to 6h following an incomplete, C2 hemisection (C2Hx). Electrophysiological mapping of the ventrolateral medulla showed a reorganization of inspiratory and expiratory sites ipsilateral to injury. These changes included i) decreased respiratory activity within the caudal ventral respiratory group (cVRG; location of bulbospinal expiratory neurons); ii) increased proportion of expiratory phase activity within the rostral ventral respiratory group (rVRG; location of inspiratory bulbo-spinal neurons); iii) increased respiratory activity within ventral reticular nuclei, including lateral reticular (LRN) and paragigantocellular (LPGi) nuclei. We conclude that disruption of descending and ascending connections between the medulla and spinal cord leads to immediate functional reorganization within the supraspinal respiratory network, including neurons within the ventral respiratory column and adjacent reticular nuclei.
呼吸功能受损是高位颈脊髓损伤（SCI）的一个毁灭性后果，这是由于支配膈肌（呼吸的主要肌肉）的膈运动神经元部分或完全去神经支配所致。因此，颈椎水平损伤的患者常常依赖辅助通气，且易发生继发性并发症。然而，越来越多的证据表明损伤后呼吸功能有有限的自发恢复，这证明了呼吸网络的神经可塑性潜力。尽管许多研究已表明脊髓水平存在这种可塑性，但对于脊髓损伤后脊髓以上水平发生的变化却知之甚少。本研究的目的是确定高位颈脊髓损伤后急性（>4小时）延髓呼吸神经元的功能重组情况。实验在去大脑、未麻醉、迷走神经完整且人工通气的大鼠身上进行。在这种制备状态下，在不完全性C2半横断（C2Hx）后4至6小时内观察到同侧膈神经活动的自发恢复。对延髓腹外侧进行电生理图谱分析显示，损伤同侧的吸气和呼气位点发生了重组。这些变化包括：i）尾侧腹侧呼吸组（cVRG；延髓脊髓呼气神经元的位置）内的呼吸活动减少；ii）头侧腹侧呼吸组（rVRG；吸气性延髓脊髓神经元的位置）内呼气相活动的比例增加；iii）腹侧网状核内的呼吸活动增加，包括外侧网状核（LRN）和旁巨细胞网状核（LPGi）。我们得出结论，延髓与脊髓之间下行和上行连接的中断导致脊髓以上呼吸网络内立即发生功能重组，包括腹侧呼吸柱和相邻网状核内的神经元。
