APPRAISAL AND RESTORATION OF RESPIRATORY FUNCTION FOLLOWING ACUTE AND CHRONIC SPINAL CORD TRAUMA
Cervical spinal cord injury typically causes robust detrimental effects to respiratory motor function. We provide evidence demonstrating that these profound effects persist from acute to chronic time points across divergent injury models. In our hands, a lateral C2 hemisection (C2Hx) causes complete paralysis of the ipsilateral hemidiaphragm with no endogenous recovery up to 1.5 years following the initial trauma. This may be caused by the reduced expression of serotonergic signaling and the up-regulation of the glial scar, limiting plasticity. A lateral C3 contusion injury (C3C) produces a more extensive lesion and similar anatomical alterations to the C2Hx. However, due to the presence of spared tissue, little functional deficit is observed through both electromyography and plethysmography. Indeed, it is only when isolated that these contused pathways are shown to be insufficient in maintaining respiratory activity. Nevertheless, we show evidence that ventilatory pattern variability may be used as a respiratory bio-marker to determine the extent of injury in real time following cervical contusion and monitor treatment outcomes. Further, in modifying the inhibitory extracellular matrix we demonstrate that respiratory paralysis can be alleviated. Up to 1.5 years following C2Hx, a single injection of chondroitinase ABC (ChABC) into the phrenic motor nucleus can mediate the robust restoration of diaphragm function. Similarly, four simultaneous ChABC injections into the cervical spinal cord following acute and sub-chronic C3C can strengthen the damaged bulbospinal pathways ensuring that they alone are able to maintain respiratory function. Collectively, these exciting results further our comprehension of cervical injuries and their effects upon respiratory motor function. They hold the potential to aid development of a specific and personalized clinical treatment strategy for respiratory dysfunction following both acute and chronic cervical spinal cord injury.
P.M. Warren1,4, S.C. Steiger1, C. Campanaro2, P.M. MacFarlane3, F.J. Jacono2, J. Silver4 & W.J. Alilain1
MetroHealth Medical Centre, 2 Division of Pulmonary, Critical Care and Sleep Medicine, 3 Dept. of Pediatrics, Rainbow Babies & Children’s Hospital and 4 Dept. of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio
Read more about Pippa Warren’s research work HERE.