Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury

• Published in: Neuroscience research Vol. 172; pp. 13 - 25
• Main Authors: Zhu, Yicheng, Uezono, Naohiro, Yasui, Tetsuro, Nakajo, Masahide, Nagai, Tatsuya, Wang, Dengli, Nishibori, Masahiro, Nakashima, Kinichi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.11.2021
• Subjects: Axon regeneration; Contusion injury; Epothilone B; Functional recovery; High Mobility Group Box-1; Spinal cord injury; Epothilone B; BBB; CNS; HMGB1; Spinal cord injury; BW; Axon regeneration; Contusion injury; High Mobility Group Box-1; ChAT; TLR; PBS; CST; Epo B; BMS; i.p; mAb; BSCB; GFAP; RST; Functional recovery; TNF-α; SCI; 5-HT; RRID; hiPSC-NSCs
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2021.04.002

•Combinatorial treatment with anti-HMGB1 mAb and Epo B improves locomotion recovery after spinal cord injury.•Epo B facilitates axon outgrowth only in combination with anti-HMGB1 mAb.•Intraspinal neurons play a critical role in the combinatorial treatment.•Our findings provide a new strategy for SCI treatment without cell transplantation. Spinal cord injury (SCI) causes motor and sensory deficits and is currently considered an incurable disease. We have previously reported that administration of anti-High Mobility Group Box-1 monoclonal antibody (anti-HMGB1 mAb) preserved lesion area and improved locomotion recovery in mouse model of SCI. In order to further enhance the recovery, we here examined combinatorial treatment of anti-HMGB1 mAb and epothilone B (Epo B), which has been reported to promote axon regeneration. This combinatorial treatment significantly increased hindlimb movement compared with anti-HMGB1 mAb alone, although Epo B alone failed to increase functional recovery. These results are in agreement with that anti-HMGB1 mAb alone was able to decrease the lesion area spreading and increase the surviving neuron numbers around the lesion, whereas Epo B facilitated axon outgrowth only in combination with anti-HMGB1 mAb, suggesting that anti-HMGB1 mAb-dependent tissue preservation is necessary for Epo B to exhibit its therapeutic effect. Taken together, the combinatorial treatment can be considered as a novel and clinically applicable strategy for SCI.