High-Mobility Group Box 1 (HMGB1) Is Elevated Systemically in Persons with Acute or Chronic Traumatic Spinal Cord Injury.
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 0-3 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.
1 Department of Autoimmune and Musculoskeletal Disorders, North Shore University Hospital , Northwell Health, Manhasset, New York.
Angelos
A
Papatheodorou
2 Department of Physical Medicine and Rehabilitation, North Shore University Hospital , Northwell Health, Manhasset, New York.
Adam
A
Stein
3 Department of Surgery, North Shore University Hospital , Northwell Health, Manhasset, New York.
Matthew
M
Bank
4 Department of Molecular Medicine, Hofstra Northwell School of Medicine, North Shore University Hospital , Northwell Health, Manhasset, New York.
Cristina P
CP
Sison
2 Department of Physical Medicine and Rehabilitation, North Shore University Hospital , Northwell Health, Manhasset, New York.
Katie
K
Gibbs
5 Litwin-Zucker Research Center for the Study of Alzheimer's Disease, the Feinstein Institute for Medical Research, North Shore University Hospital , Northwell Health, Manhasset, New York.
Peter
P
Davies
1 Department of Autoimmune and Musculoskeletal Disorders, North Shore University Hospital , Northwell Health, Manhasset, New York.|2 Department of Physical Medicine and Rehabilitation, North Shore University Hospital , Northwell Health, Manhasset, New York.|4 Department of Molecular Medicine, Hofstra Northwell School of Medicine, North Shore University Hospital , Northwell Health, Manhasset, New York.
Ona
O
Bloom
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002574:Cervical Vertebrae; D002908:Chronic Disease; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013119:Spinal Cord Injuries / Q000097:blood* / Q000175:diagnosis*; D013904:Thoracic Vertebrae; D055815:Young Adult
D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human
damage-associated molecular pattern; high mobility group box 1; inflammation; spinal cord injury
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