Breathing patterns after mid-cervical spinal contusion in rats

Abstract

Respiratory failure is the leading cause of death after cervical spinal injury. We hypothesized that incomplete cervical spinal injuries would alter respiratory pattern and initiate plasticity in the neural control of breathing. Further, we hypothesized that the severity of cervical spinal contusion would correlate with changes in breathing pattern. Fourteen days after C4–C5 contusions, respiratory frequency and tidal volume were measured in unanesthetized Sprague Dawley rats in a whole body plethysmograph. Phrenic motor output was monitored in the same rats which were anesthetized, vagotomized, paralyzed and ventilated to eliminate and/or control sensory feedback that could alter breathing patterns. The extent of spinal injury was approximated histologically by measurements of the injury-induced cyst area in transverse sections; cysts ranged from 2 to 28% of spinal cross-sectional area, and had a unilateral bias. In unanesthetized rats, the severity of spinal injury correlated negatively with tidal volume (R2=0.85; p<0.001) and positively with breathing frequency (R2=0.65; p<0.05). Thus, the severity of C4–C5 spinal contusion dictates post-injury breathing pattern. In anesthetized rats, phrenic burst amplitude was decreased on the side of injury, and burst frequency correlated negatively with contusion size (R2=0.51; p<0.05). A strong correlation between unanesthetized breathing pattern and the pattern of phrenic bursts in anesthetized, vagotomized and ventilated rats suggests that changes in respiratory motor output after spinal injury reflect, at least in part, intrinsic neural mechanisms of CNS plasticity initiated by injury.

The impact of spinal cord injury on breathing during sleep

“…Simon et al (1995) showed that individuals with high cervical SCI initiated inspiratory electromyogram (EMG) activity at a lower end-tidal CO 2 as compared to able-bodied controls (i.e., after SCI there was a lower CO 2 recruitment threshold). A similar finding has been reported in a rat model (Golder et al, 2011). A reduction in the CO 2 “apneic threshold” after SCI could reflect an increase in the CO 2 sensitivity of respiratory neurons and/or networks.…”

Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

“…Several contusion models at mid-cervical levels (C3, C4, C5) that show chronic abnormalities in respiratory parameters have been developed in the rat. [22][23][24][25] The extension of a contusion injury model to the mouse provides opportunities for manipulating genes of interest and for evaluating their role in relevant outcome measures affected by cervical spinal contusion such as forelimb motor function, respiratory function, and neuropathic pain.…”

“…In addition, this model allows for the use of genetically modified animals for exploring the function of specific genes in the pathophysiology of respiratory motor neuron degeneration and functional respiratory compromise following cervical SCI. [19][20][21][22][23] Methods…”

Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons

“…Respiratory deficits following cervical SCI have been studied using various animal models that impair ventilation without the need for chronic mechanical ventilatory support, including midline (el-Bohy et al, 1998; Golder et al, 2011; Lane et al, 2012) vs. unilateral contusion (Alvarez-Argote et al, 2015; Baussart et al, 2006; Nicaise et al, 2013; Nicaise et al, 2012a; Nicaise et al, 2012b), or transection (Imagita et al, 2015). A well-established model of SCI, spinal hemisection of the C2 segment of the cervical spinal cord (SH) abolishes descending neural drive to ipsilateral phrenic motoneurons, transiently interrupting ipsilateral phrenic motoneuron activity and inducing DIAm paralysis (Fuller et al, 2006; Goshgarian, 2003; Gransee et al, 2013, 2015; Mantilla et al, 2013a; Mantilla et al, 2013b; Porter, 1895).…”