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

Publication date: Available online 28 March 2018
Source:Neuroscience Research
Author(s): Masahide Nakajo, Naohiro Uezono, Hideyuki Nakashima, Hidenori Wake, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima
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 hours) and 6 hours after) SCI dramatically improves functional recovery after SCI in mice. However, when considering clinical application, 0 hours after SCI is not practical. Therefore, in this study, we examined the therapeutic time window of the mAb administration. Injection at 3 hours after SCI significantly improved the functional recovery comparably to injection immediately after SCI, while injection at 6 hours was less effective, and injection at 9 or 12 hours had no therapeutic effect. We also found beneficial effects of injection at 3 hours 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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