Holmes Taylor C, Popp Nicole M, Hintz Carley F, Dobrzycki Isabell, Schmitz Carolyn J, Schwichtenberg Kaylyn A, Gonzalez-Rothi Elisa J, Sundberg Christopher W, Streeter Kristi A
Exercise and Rehabilitation Science Program, Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin, United States.
Athletic and Human Performance Research Center, Marquette University, Milwaukee, Wisconsin, United States.
J Appl Physiol (1985). 2024 Jul 1;137(1):166-180. doi: 10.1152/japplphysiol.00040.2024. Epub 2024 Jun 13.
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). 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.
通过单性别研究,C2半横断(C2Hx)后的呼吸功能缺陷已有充分记录。尽管卵巢性激素能促进雌性大鼠在C2Hx术后2周观察到的呼吸恢复增强,但在慢性时间点性别是否影响自发呼吸恢复仍不清楚。我们进行了一项纵向研究,以全面描述C2Hx术后8周基于性别的呼吸神经肌肉恢复情况。我们记录了清醒、活动动物的通气和慢性膈肌肌电图(EMG)输出、麻醉动物的膈神经运动输出,并对慢性损伤的雄性和雌性啮齿动物进行了膈肌肌肉组织学检查。我们的结果表明,在亚急性和慢性时间点,雌性大鼠的潮气量和分钟通气量恢复程度高于雄性。损伤后所有时间点,两性在清醒时的平静呼吸膈肌EMG振幅和膈神经运动振幅相似。我们的数据还表明,与雄性相比,雌性大鼠在自发深呼吸(如叹息)时同侧膈肌EMG振幅的降低幅度更大。最后,我们发现雌性而非雄性损伤同侧快速易疲劳纤维存在萎缩和重塑的证据。据我们所知,本文所呈现的数据是第一项报告慢性C2Hx后自发呼吸恢复和膈肌肌肉形态存在性别差异的研究。这些数据强调了研究两性对于为脊髓损伤(SCI)后呼吸恢复提供循证治疗干预的必要性。针对慢性C2半横断,雌性啮齿动物在平静呼吸时的潮气量比雄性增加。雌性在自发深呼吸(如叹息)时膈肌肌电图(EMG)振幅降低幅度更大,且快速易疲劳的膈肌纤维存在萎缩和重塑。鉴于大多数康复干预发生在损伤的亚急性至慢性阶段,这些结果突出了脊髓损伤后开发和评估治疗方法时考虑性别的重要性。