TY - JOUR
T1 - Therapeutic time window of anti-high mobility group box-1 antibody administration in mouse model of spinal cord injury
AU - Nakajo, Masahide
AU - Uezono, Naohiro
AU - Nakashima, Hideyuki
AU - Wake, Hidenori
AU - Komiya, Setsuro
AU - Nishibori, Masahiro
AU - Nakashima, Kinichi
N1 - Funding Information:
We thank T. Imamura and S. Katada for valuable discussions; Y. Nakagawa for excellent secretarial assistance; and E. Nakajima for proofreading the manuscript. We are very grateful to A. Sakai, J. Takouda, K. Irie, T. Irie, R. Yamashita, T. Nagai, and Y. Zhu for technical help. We also thank T. Miura for providing access to a fluorescence microscope (Keyence BZ9000) and for technical support from the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This work was funded by JSPS KAKENHI ( 16H06527 ), the Mitsubishi Foundation , and the Suzuken Memorial Foundation to K.N., and by a Translational Research Network Program (No. H27 seeds B-8-1) from AMED to M.N.
Funding Information:
We thank T. Imamura and S. Katada for valuable discussions; Y. Nakagawa for excellent secretarial assistance; and E. Nakajima for proofreading the manuscript. We are very grateful to A. Sakai, J. Takouda, K. Irie, T. Irie, R. Yamashita, T. Nagai, and Y. Zhu for technical help. We also thank T. Miura for providing access to a fluorescence microscope (Keyence BZ9000) and for technical support from the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This work was funded by JSPS KAKENHI (16H06527), the Mitsubishi Foundation, and the Suzuken Memorial Foundation to K.N. and by a Translational Research Network Program (No. H27 seeds B-8-1) from AMED to M.N.
Publisher Copyright:
© 2018 Elsevier B.V. and Japan Neuroscience Society
PY - 2019/4
Y1 - 2019/4
N2 - 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.
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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U2 - 10.1016/j.neures.2018.03.004
DO - 10.1016/j.neures.2018.03.004
M3 - Article
C2 - 29604317
AN - SCOPUS:85045016049
SN - 0168-0102
VL - 141
SP - 63
EP - 70
JO - Neuroscience Research
JF - Neuroscience Research
ER -