Diaphragm Muscle Function Following Mid‐Cervical Contusion Injury in Rats

Abstract

Mid‐cervical spinal cord contusion injury results in tissue damage, disruption of spinal pathways, and motoneuron loss. Phrenic motoneurons located in C3–5 segments of the cervical spinal cord innervate the diaphragm muscle (DIAm), and unilateral C4 contusion results in loss of 40–50% of motoneurons ipsilateral to the injury (~25% of the total motoneuron pool). Over time after unilateral C4 spinal cord contusion injury, DIAm electromyography (EMG) increases both contralateral and ipsilateral to the side of injury, suggesting compensation due to an increased activation of the surviving motoneurons. However, whether C4 contusion impairs the ability of the DIAm to accomplish higher force motor behaviors is unknown. Transdiaphragmatic pressure (Pdi) was measured across motor behaviors over time after unilateral C4 contusion injury. Maximum Pdi (Pdimax) was elicited by bilateral phrenic nerve stimulation at 7 days post‐injury. We hypothesized that Pdimax is reduced following C4 mid‐cervical contusion injury, which will constrain the Pdi generated during different motor behaviors. Since ventilatory behaviors of the DIAm require <50% Pdimax, we further hypothesized that Pdi generated during ventilatory behaviors of the DIAm is not impaired after unilateral C4 mid‐cervical spinal cord contusion injury. In support of our hypothesis, we observed that Pdimax was reduced by ~25% after C4 mid‐cervical spinal cord contusion injury compared to a laminectomy control group. This decrease in Pdimax is consistent with the extent of phrenic motoneuron loss following contusion injury. We also found that during both eupnea (quiet breathing) and breathing stimulated by 10% O2 (hypoxia) and 5% CO2 (hypercapnia), Pdi generation was unimpaired by C4 mid‐cervical spinal cord contusion injury, again consistent with the lower force requirement of these ventilatory motor behaviors. Prior to injury, Pdi generated during airway occlusion was ~40% of Pdimax. One day following contusion injury, the Pdi amplitude during airway occlusion was reduced from ~30 cm H2O to ~20 cm, but this reduction was completely reversed by 7 days post‐injury. The reduction in Pdi amplitude at one day post‐injury cannot be attributed to the ~25% loss of phrenic motoneurons, and thus, may reflect a disruption of input to phrenic motoneurons or acute inflammation of their surrounding milieu. Over time after injury, changes in the balance between inhibition and excitation may result in recovery of higher‐force behaviors.Support or Funding InformationFunded by NIH R01‐HL096750 and T32‐HL105355This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Aging affects the number and morphological heterogeneity of rat phrenic motor neurons and phrenic motor axons

“…More forceful straining expulsive DIAm behaviors are far less frequent and require recruitment of FF motor units (Fogarty & Sieck, 2019a , 2019b ; Sieck & Fournier, 1989 ). For motor units in the DIAm, these functional distinctions are relevant under pathophysiological conditions affecting PhMNs and/or DIAm muscle fibers, such as early‐onset spasticity (Brandenburg et al, 2020 ; Fogarty et al, 2022 ; Fogarty, Brandenburg, & Sieck, 2020 ), cervical spinal cord injury (Khurram et al, 2019 ; Miyata et al, 1995 ) and aging (Fogarty, Gonzalez Porras, et al, 2019 ; Fogarty, Mantilla, & Sieck, 2019 ; Fogarty, Marin Mathieu, et al, 2020 ; Fogarty, Omar, et al, 2018 ; Gosselin et al, 1994 ; Khurram et al, 2018 ).…”