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Cervical excitatory neurons sustain breathing after spinal cord injury

机译:颈脊髓神经元在脊髓损伤后维持呼吸

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摘要

Dysfunctional breathing is the main cause of morbidity and mortality after traumatic injury of the cervical spinal cord(1,2) and often necessitates assisted ventilation, thus stressing the need to develop strategies to restore breathing. Cervical interneurons that form synapses on phrenic motor neurons, which control the main inspiratory muscle, can modulate phrenic motor output and diaphragmatic function(3-5). Here, using a combination of pharmacogenetics and respiratory physiology assays in different models of spinal cord injury, we show that mid-cervical excitatory interneurons are essential for the maintenance of breathing in mice with non-traumatic cervical spinal cord injury, and are also crucial for promoting respiratory recovery after traumatic spinal cord injury. Although these interneurons are not necessary for breathing under normal conditions, their stimulation in non-injured animals enhances inspiratory amplitude. Immediately after spinal cord injury, pharmacogenetic stimulation of cervical excitatory interneurons restores respiratory motor function. Overall, our results demonstrate a strategy to restore breathing after central nervous system trauma by targeting a neuronal subpopulation.
机译:呼吸功能不全是颈脊髓外伤后发病和死亡的主要原因(1,2),并且通常需要辅助通气,因此强调需要制定恢复呼吸的策略。颈inter神经元在motor运动神经元上形成突触,控制着主吸气肌,可以调节motor运动输出和diaphragm肌功能(3-5)。在这里,在不同的脊髓损伤模型中,结合使用药理遗传学和呼吸生理学分析,我们显示中颈兴奋性中间神经元对于维持非创伤性颈脊髓损伤的小鼠的呼吸至关重要,并且对于促进脊髓损伤后的呼吸恢复。尽管这些中间神经元在正常条件下不是呼吸所必需的,但是它们在未受伤的动物中的刺激会增加吸气幅度。脊髓损伤后,立即通过药理遗传学刺激颈兴奋性神经元恢复呼吸运动功能。总体而言,我们的结果证明了针对神经元亚群的中枢神经系统创伤后恢复呼吸的策略。

著录项

  • 来源
    《Nature》 |2018年第7727期|419-422|共4页
  • 作者单位

    Univ Hlth Network, Krembil Res Inst, Toronto, ON, Canada;

    Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada;

    Univ Hlth Network, Krembil Res Inst, Toronto, ON, Canada;

    St Michaels Hosp, Toronto, ON, Canada;

    Univ Hlth Network, Krembil Res Inst, Toronto, ON, Canada;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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