Respiratory function following bilateral mid-cervical contusion injury in the adult rat

Abstract The consequences of spinal cord injury (SCI) are often viewed as the result of white matter damage. However, injuries occurring at any spinal level, especially in cervical and lumbar enlargement regions, also entail segmental neuronal loss. Yet, the contributions of gray matter injury and plasticity to functional outcomes are poorly understood. The present study addressed this issue by investigating changes in respiratory function following bilateral C3/C4 contusion injuries at the level of the phrenic motoneuron (PhMN) pool which in the adult rat extends from C3 to C5/6 and provides innervation to the diaphragm. Despite extensive white and gray matter pathology associated with two magnitudes of injury severity, ventilation was relatively unaffected during both quiet breathing and respiratory challenge (hypercapnia). On the other hand, bilateral diaphragm EMG recordings revealed that the ability to increase diaphragm activity during respiratory challenge was substantially, and chronically, impaired. This deficit has not been seen following predominantly white matter lesions at higher cervical levels. Thus, the impact of gray matter damage relative to PhMNs and/or interneurons becomes evident during conditions associated with increased respiratory drive. Unaltered ventilatory behavior, despite significant deficits in diaphragm function, suggests compensatory neuroplasticity involving recruitment of other spinal respiratory networks which may entail remodeling of connections. Transynaptic tracing, using pseudorabies virus (PRV), revealed changes in PhMN-related interneuronal labeling rostral to the site of injury, thus offering insight into the potential anatomical reorganization and spinal plasticity following cervical contusion. Abbreviations BDA, biotin dextran amine; C#, spinal cervical segment #; C2Hx, C2 lateral hemisection; CPP, crossed-phrenic phenomenon; diaEMG, diaphragm electromyography; f, breathing frequency; KD, kilodynes; PEF, peak expiratory flow; PhMN, phrenic motoneuron; PIF, peak inspiratory flow; PRV, pseudorabies virus; SpO2, blood oxygen saturation; E, minute ventilation; VRC, ventral respiratory column; VT, tidal volume Keywords Spinal cord injury; Respiration; Plasticity; Interneuron; Pseudorabies virus; Contusion

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