Abstract：
Respiratory deficits after C2 hemisection (C2Hx) have been well documented through single-sex investigations. Although ovarian sex hormones enable enhanced respiratory recovery observed in females 2 wk post-C2Hx, it remains unknown if sex impacts spontaneous respiratory recovery at chronic time points. We conducted a longitudinal study to provide a comprehensive sex-based characterization of respiratory neuromuscular recovery for 8 wk after C2Hx. We recorded ventilation and chronic diaphragm electromyography (EMG) output in awake, behaving animals, phrenic motor output in anesthetized animals, and performed diaphragm muscle histology in chronically injured male and female rodents. Our results show that females expressed a greater recovery of tidal volume and minute ventilation compared with males during subacute and chronic time points. Eupneic diaphragm EMG amplitude during wakefulness and phrenic motor amplitude are similar between sexes at all time points after injury. Our data also suggest that females have a greater reduction in ipsilateral diaphragm EMG amplitude during spontaneous deep breaths (e.g., sighs) compared with males. Finally, we show evidence for atrophy and remodeling of the fast, fatigable fibers ipsilateral to injury in females, but not in males. To our knowledge, the data presented here represent the first study to report sex-dependent differences in spontaneous respiratory recovery and diaphragm muscle morphology following chronic C2Hx. These data highlight the need to study both sexes to inform evidence-based therapeutic interventions in respiratory recovery after spinal cord injury (SCI).NEW & NOTEWORTHY In response to chronic C2 hemisection, female rodents display increased tidal volume during eupneic breathing compared with males. Females show a greater reduction in diaphragm electromyography (EMG) amplitude during spontaneous deep breaths (e.g., sighs) and atrophy and remodeling of fast, fatigable diaphragm fibers. Given that most rehabilitative interventions occur in the subacute to chronic stages of injury, these results highlight the importance of considering sex when developing and evaluating therapeutics after spinal cord injury.
摘要：
C2半切（C2Hx）后的呼吸缺陷已通过单性别调查得到了充分记录。尽管在C2Hx后两周观察到的女性卵巢性激素可以增强呼吸恢复，性别是否影响慢性时间点的自主呼吸恢复仍不得而知.我们进行了一项纵向研究，以提供C2Hx后8周呼吸神经肌肉恢复的基于性别的全面表征。我们记录了清醒行为动物的通气和慢性膈肌电图（EMG）输出，麻醉动物的膈运动输出，并对慢性受伤的雄性和雌性啮齿动物进行了diaphragm肌组织学检查。我们的结果表明，在亚急性和慢性时间点，与男性相比，女性的潮气量和每分钟通气量恢复更大。在受伤后的所有时间点，清醒期间的Eupneic隔膜EMG振幅和the运动振幅在性别之间相似。我们的数据还表明，在自发深呼吸期间，女性的同侧膈肌肌电图幅度降低更大（例如，叹息）与男性相比。最后,我们显示了萎缩和快速重塑的证据，女性受伤同侧的易疲劳纤维，但不是男性。据我们所知,本文提供的数据代表了第一项报告慢性C2Hx后自发呼吸恢复和膈肌形态的性别依赖性差异的研究。这些数据强调了研究两性的必要性，以告知SCI后呼吸恢复的循证治疗干预措施。
