Therapeutic time window of anti-high mobility group box-1 antibody administration in mouse model of spinal cord injury

Neurosci Res. 2019 Apr:141:63-70. doi: 10.1016/j.neures.2018.03.004. Epub 2018 Mar 28.


Spinal cord injury (SCI) is a devastating neurologic disorder that often leads to permanent disability, and there is no effective treatment for it. High mobility group box-1 (HMGB1) is a damage-associated molecular protein that triggers sterile inflammation upon injuries. We have previously shown that two administrations of neutralizing monoclonal antibody (mAb) against HMGB1 (immediately after (0 h) and 6 h after) SCI dramatically improves functional recovery after SCI in mice. However, when considering clinical application, 0 h after SCI is not practical. Therefore, in this study, we examined the therapeutic time window of the mAb administration. Injection at 3 h after SCI significantly improved the functional recovery comparably to injection immediately after SCI, while injection at 6 h was less effective, and injection at 9 or 12 h had no therapeutic effect. We also found beneficial effects of injection at 3 h after injury on blood-spinal cord barrier maintenance, inflammatory-related gene expression and preservation of the damaged spinal cord tissue. Taken together, our results suggest that a single administration of anti-HMGB1 mAb within a proper time window could be a novel and potential therapeutic strategy for SCI.

Keywords: Blood-spinal-cord barrier; HMGB1; Spinal cord injury; Time window.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Disease Models, Animal
  • Female
  • HMGB1 Protein / administration & dosage*
  • HMGB1 Protein / immunology
  • Mice, Inbred C57BL
  • Myelitis / etiology
  • Myelitis / prevention & control
  • Recovery of Function
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / immunology


  • Antibodies, Monoclonal
  • HMGB1 Protein
  • HMGB1 protein, mouse