Sex differences in spontaneous respiratory recovery following chronic C2 hemisection.

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.

Diaphragm stimulation elicits phrenic afferent-induced neuromuscular plasticity.

We hypothesized that activation of phrenic afferents induces diaphragm motor plasticity. In anesthetized and spontaneously breathing rats we delivered 40 Hz, low threshold (twitch and 1.5X twitch threshold), inspiratory-triggered stimulation to the left hemidiaphragm for 30 min to activate ipsilateral phrenic afferents. Diaphragm amplitude ipsilateral and contralateral to stimulation were increased for 60 min following both currents compared to time controls not receiving stimulation. Diaphragm stimulation was repeated in laminectomy controls or following a unilateral C3-C6 dorsal rhizotomy to eliminate phrenic afferent volleys. Laminectomy controls expressed neuromuscular plasticity post-stimulation. In contrast, ipsilateral and contralateral diaphragm amplitude following dorsal rhizotomy was lower than laminectomy controls and no different than time controls, suggesting diaphragm motor plasticity was not induced post-rhizotomy. Our results indicate that diaphragm stimulation induces a novel form of plasticity in the phrenic motor system which requires phrenic afferent activation. Respiratory motor plasticity elicited by diaphragm stimulation may have value as a therapeutic strategy to improve diaphragm output in neuromuscular conditions.

Reduced effects of tendon vibration with increased task demand during active, cyclical ankle movements.

Tendon vibration can alter proprioceptive feedback, one source of sensory information which humans can use to produce accurate movements. However, the effects of tendon vibration during functional movement vary depending on the task. For example, ankle tendon vibration has considerably smaller effects during walking than standing posture. The purpose of this study was to test whether the effects of ankle tendon vibration are predictably influenced by the mechanical demands of a task, as quantified by peak velocity. Twelve participants performed symmetric, cyclical ankle plantar flexion/dorsiflexion movements while lying prone with their ankle motion unconstrained. The prescribed movement period (1, 3 s) and peak-to-peak amplitude (10°, 15°, 20°) were varied across trials; shorter movement periods or larger amplitudes increased the peak velocity. In some trials, vibration was continuously and simultaneously applied to the right ankle plantar flexor and dorsiflexor tendons, while the left ankle tendons were never vibrated. The vibration frequency (40, 80, 120, 160 Hz) was varied across trials. During trials without vibration, participants accurately matched the movement of their ankles. The application of 80 Hz vibration to the right ankle tendons significantly reduced the amplitude of right ankle movement. However, the effect of vibration was smaller during more mechanically demanding (i.e., higher peak velocity) movements. Higher vibration frequencies had larger effects on movement accuracy, possibly due to parallel increases in vibration amplitude. These results demonstrate that the effects of ankle tendon vibration are dependent on the mechanical demand of the task being performed, but cannot definitively identify the underlying physiological mechanism.