Journal
JOURNAL OF NEUROTRAUMA
Volume 34, Issue 3, Pages 746-754Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2016.4596
Keywords
damage-associated molecular pattern; high mobility group box 1; inflammation; spinal cord injury
Funding
- Craig H. Neilsen Foundation
- New York State Empire Clinical Research Program
- National Center for Research Resources (NCRR) [M01RR018535]
- National Institutes of Health (NIH)
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Inflammation in traumatic spinal cord injury (SCI) has been proposed to promote damage acutely and oppose functional recovery chronically. However, we do not yet understand the signals that initiate or prolong inflammation in persons with SCI. High-Mobility Group Box 1 (HMGB1) is a potent systemic inflammatory cytokine-or damage-associated molecular pattern molecule (DAMP)-studied in a variety of clinical settings. It is elevated in pre-clinical models of traumatic spinal cord injury (SCI), where it promotes secondary injury, and strategies that block HMGB1 improve functional recovery. To investigate the potential translational relevance of these observations, we measured HMGB1 in plasma from adults with acute (<= 1 week post-SCI, n = 16) or chronic (>= 1 year post-SCI, n = 47) SCI. Plasma from uninjured persons (n = 51) served as controls for comparison. In persons with acute SCI, average HMGB1 levels were significantly elevated within 03 days post-injury (6.00 +/- 1.8 ng/mL, mean +/- standard error of the mean [SEM]) or 4-7 (6.26 +/- 1.3 ng/mL, mean +/- SEM), compared with controls (1.26 +/- 0.24 ng/mL, mean +/- SEM; p <= 0.001 and p <= 0.01, respectively). In persons with chronic SCI who were injured for 15 +/- 1.5 years (mean +/- SEM), HMGB1 also was significantly elevated, compared with uninjured persons (3.7 +/- 0.69 vs. 1.26 +/- 0.24 ng/mL, mean +/- SEM; p <= 0.0001). Together, these data suggest that HMGB1 may be a common, early, and persistent danger signal promoting inflammation in individuals with SCI.
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