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Permanent diaphragmatic deficits and spontaneous respiratory plasticity in a mouse model of incomplete cervical spinal cord injury
Respiratory Physiology & Neurobiology ( IF 1.9 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.resp.2020.103568
Pauline Michel-Flutot , Arnaud Mansart , Therese B. Deramaudt , Isley Jesus , Kun-Ze Lee , Marcel Bonay , Stéphane Vinit

High spinal cord injuries (SCI) lead to permanent respiratory insufficiency, and the search for new therapeutics to restore this function is essential. To date, the most documented preclinical model for high SCI is the rat cervical C2 hemisection. However, molecular studies with this SCI model are limited due to the poor availability of genetically modified specimens. The aim of this work was to evaluate the pathophysiology of respiratory activity following a cervical C2 injury at different times post-injury in a C57BL/6 mouse model. No significant spontaneous recovery of diaphragmatic activity was observed up to 30 days post-injury in eupneic condition. However, during a respiratory challenge, i.e. mild asphyxia, a partial restoration of the injured diaphragm was observed at 7 days post-injury, corresponding to the crossed phrenic phenomenon. Interestingly, the diaphragmatic recording between 2 respiratory bursts on the injured side showed an amplitude increase between 1–7 days post-injury, reflecting a change in phrenic motoneuronal excitability. This increase in inter-burst excitability returned to pre-injured values when the crossed phrenic phenomenon started to be effective at 7 days post-injury. Taken together, these results demonstrate the ability of the mouse respiratory system to express long-lasting plasticity following a C2 cervical hemisection and genetically modified animals can be used to study the pathophysiological effects on these plasticity phenomena.



中文翻译:

不完全颈脊髓损伤小鼠模型中的永久性膈肌功能缺损和自发呼吸可塑性

高位脊髓损伤 (SCI) 会导致永久性呼吸功能不全,因此必须寻找新的疗法来恢复这种功能。迄今为止,记录最多的高 SCI 临床前模型是大鼠颈椎 C2 半切术。然而,由于转基因标本的可用性较差,使用这种 SCI 模型进行的分子研究受到限制。这项工作的目的是评估 C57BL/6 小鼠模型受伤后不同时间颈椎 C2 损伤后呼吸活动的病理生理学。在 euneic 状态下,在受伤后 30 天未观察到明显的膈肌活动自发恢复。然而,在呼吸挑战期间,轻度窒息,在受伤后 7 天观察到受伤的膈肌部分恢复,对应于交叉膈现象。有趣的是,受伤侧 2 次呼吸爆发之间的膈肌记录显示在受伤后 1-7 天之间振幅增加,反映了膈运动神经元兴奋性的变化。当交叉膈现象在受伤后 7 天开始有效时,这种爆发间兴奋性的增加恢复到受伤前的值。总之,这些结果证明了小鼠呼吸系统在 C2 颈椎半切术后表达持久可塑性的能力,转基因动物可用于研究对这些可塑性现象的病理生理学影响。

更新日期:2020-11-05
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