While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in a rat model. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expression of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

Spinal cord injury (SCI) is associated with an increased susceptibility to infections, such as pneumonia, which is the leading cause of death in these patients. This phenomenon is referred to as SCI immune deficiency syndrome (SCI-IDS), and has been shown to be more prevalent after high-level transection in preclinical SCI models. Despite the high prevalence of contusion SCIs, the effects of this etiology have not been studied in the context of SCI-IDS. Compared to transection SCIs, which involve a complete loss of supraspinal input and lead to the disinhibition of spinally-generated activity, contusion SCIs may cause significant local deafferentation, but only a partial disruption of sympathetic tone below the level of injury. In this work, we investigate the effects of thoracic (T6-7) and cervical (C6-7) moderate–severe contusion SCIs on the spleen by characterizing splenic norepinephrine (NE) and cortisol (CORT), caspase-3, and multiple inflammation markers at 3- and 7-days post-SCI. In contrary to the literature, we observe an increase in splenic NE and CORT that correspond to an increase in caspase-3 after thoracic SCI relative to cervical SCI. Further, we found differences in expression of leptin, eotaxin, IP-10, and IL-18 that implicate alterations in splenocyte recruitment and function. These results suggest that incomplete SCI drastically alters the level-dependence of SCI-IDS.

While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in the rat. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expressions of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.