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Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury

1
Division of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada
2
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
3
Spinal Program, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(8), 2167; https://doi.org/10.3390/ijms19082167
Received: 11 July 2018 / Revised: 23 July 2018 / Accepted: 23 July 2018 / Published: 25 July 2018
(This article belongs to the Special Issue Therapeutic Strategies to Spinal Cord Injury)
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Abstract

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. View Full-Text
Keywords: spinal cord injury; inflammation; plasma spinal cord injury; inflammation; plasma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hong, J.; Chang, A.; Zavvarian, M.-M.; Wang, J.; Liu, Y.; Fehlings, M.G. Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury. Int. J. Mol. Sci. 2018, 19, 2167.

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