Molecular pathology of acute spinal cord injury in middle-aged mice

The median age at which spinal cord injuries occur has steadily increased from 29 to 43 over the last several decades. Although more pre-clinical studies in aged rodents are being done to address this shift in demographics, comprehensive transcriptomic studies investigating SCI pathobiology in middle-aged mice are lacking. To address this gap in knowledge, we compared behavioral, histopathological, and transcriptional outcomes in young (2-4 months old) and middle-aged (10-12 months old) mice. In contrast to most previous studies, open field tests showed no differences in locomotor recovery between the young and middle-aged mice over a one-month period. The injury site also demonstrated similar histopathology in terms of lesion size, and numbers of macrophages and fibroblasts. Acutely after injury, proliferation of macrophages, fibroblasts, and astrocytes were also similar between the two age groups. In addition, spatial transcriptomics showed similar, transcriptionally defined regions around the injury site at 3 days post-injury. However, single cell RNA-sequencing of the cells at the injury site and surrounding spared tissue showed differences in select cell subpopulations. Taken together, our results indicate that although young and middle-aged mice display similar locomotor recovery and histopathology after SCI, changes in cell subpopulations may underlie a decline in repair mechanisms that manifest after middle age.