Faculty Collaboration Database

Sex differences in spontaneous respiratory recovery following chronic C2 hemisection. J Appl Physiol (1985) 2024 Jul 01;137(1):166-180

Date

06/13/2024

Pubmed ID

38867665

Pubmed Central ID

PMC11381122

DOI

10.1152/japplphysiol.00040.2024

Scopus ID

2-s2.0-85198681974 (requires institutional sign-in at Scopus site)   3 Citations

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.

Author List

Holmes TC, Popp NM, Hintz CF, Dobrzycki I, Schmitz CJ, Schwichtenberg KA, Gonzalez-Rothi EJ, Sundberg CW, Streeter KA

Authors

Taylor C. Holmes PhD, BS, DPT Postdoctoral Researcher 1 in the Physiology department at Medical College of Wisconsin
Chrisopher Sundberg in the CTSI department at Medical College of Wisconsin - CTSI

MESH terms used to index this publication - Major topics in bold

Animals
Cervical Cord
Diaphragm
Electromyography
Female
Male
Phrenic Nerve
Rats
Rats, Sprague-Dawley
Recovery of Function
Respiration
Sex Characteristics
Spinal Cord Injuries