Acute spinal cord injury-acquired pneumonia induces sustained lung injury in mice

Systemic immunosuppression is a devastating result of spinal cord injury (SCI), leaving many patients susceptible to infections such as pneumonia. SCI-associated pneumonia (SCI-AP) is a clinically-relevant outcome modifier associated with increased mortality and disability. While it is known that lungs become damaged after SCI, it is yet to be established how an acquired pneumonia further impacts the lungs after SCI. Using a controlled mouse model of induced spinal cord injury-associated pneumonia (SCI-AP), we quantified structural and immunological changes by comparing T9 contusive SCI with laminectomy controls, with or without pneumonia. This approach allowed us to distinguish alterations attributable to pneumonia from those resulting directly from spinal cord injury. Matching clinical onset in patients, SCI-AP was induced at 3 days post-injury. Hematoxylin & Eosin stains were performed on paraffin-embedded lung tissue at acute and chronic timepoints post-injury to assess the time course of histological changes post-infection. Structural changes in bronchial wall thickness and apoptosis within the nuclei of the epithelial walls of lung bronchioles were assessed in the lower right lung. Consistent with pneumonia onset, neutrophils were detected in the lungs. SCI-AP mice had significantly more F4/80+ macrophages in their lung tissue compared to SCI mice. Bronchial walls become thinner and contain higher cell numbers undergoing programmed cell death after SCI-AP induction. These histological changes have functional impacts on whole body metabolism, as monitored with a comprehensive monitoring system. This work demonstrates features of acute and chronic SCI-AP and its subsequent structural changes in the lung in a mouse model, and provides mechanisms that may contribute to persistent pulmonary dysfunction and increased susceptibility to respiratory complications after SCI. Further investigations are needed to see if these changes are present clinically.