Immunoglobulin G Is Increased in the Injured Spinal Cord in a Sex- and Age-Dependent Manner

There are limited studies examining age and sex as biological variables in the pathophysiology of spinal cord injury (SCI). The use of older animals and sex-balanced groups in SCI models is increasingly prioritized to better match clinical demographics. Including older animals in SCI studies is technically challenging, and outcomes are unpredictable with respect to biological and treatment responses. Incidental discoveries that are unrelated to the question under investigation often emerge while including age and sex as biological variables. When probing tissue homogenates on Western blots of 4- and 14-month-old (MO) mice, we identified a sex- and age-dependent increase in immunoglobulin G (IgG) within the spinal cords of older, 14-MO mice acutely after SCI, with females having more IgG compared with males. We further probed to determine whether differences in hemorrhage exist between sexes or ages by evaluating hemoglobin within spinal homogenates. Differences in hemoglobin between sexes and ages were not consistently observed. Because IgG was elevated in an age- and sex-dependent manner without of evidence of differences in hemorrhage, our findings point to potential pre-existing differences in IgG within mouse plasma in an age- and sex-dependent manner. This report has identified age- and sex-dependent differences in infiltrating IgG into the injured spinal cord environment that may affect injury and recovery processes. Our findings highlight that systemic contributions to SCI can be sex- and age-dependent and illustrate the value of reporting incidental discoveries.