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

Masahide Nakajo, Naohiro Uezono, Hideyuki Nakashima, Hidenori Wake, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalNeuroscience Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Spinal Cord Injuries
Antibodies
Injections
Monoclonal Antibodies
Therapeutics
Spinal Cord
Wounds and Injuries
Therapeutic Uses
Neutralizing Antibodies
Nervous System Diseases
Maintenance
Inflammation
Gene Expression
Proteins

Keywords

  • Blood-spinal-cord barrier
  • HMGB1
  • Spinal cord injury
  • Time window

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Therapeutic time window of anti-high mobility group box-1 antibody administration in mouse model of spinal cord injury. / Nakajo, Masahide; Uezono, Naohiro; Nakashima, Hideyuki; Wake, Hidenori; Komiya, Setsuro; Nishibori, Masahiro; Nakashima, Kinichi.

In: Neuroscience Research, 01.01.2018.

Research output: Contribution to journalArticle

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AB - 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.

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