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Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury
Neuroscience Research ( IF 2.9 ) Pub Date : 2021-04-18 , DOI: 10.1016/j.neures.2021.04.002
Yicheng Zhu 1 , Naohiro Uezono 1 , Tetsuro Yasui 1 , Masahide Nakajo 1 , Tatsuya Nagai 1 , Dengli Wang 2 , Masahiro Nishibori 2 , Kinichi Nakashima 1
Affiliation  

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.



中文翻译:

抗高迁移率组 Box-1 单克隆抗体和埃坡霉素 B 的联合治疗改善脊髓挫伤后的功能恢复

脊髓损伤 (SCI) 会导致运动和感觉障碍,目前被认为是一种不治之症。我们之前曾报道过,在 SCI 小鼠模型中,使用抗高迁移率组 Box-1 单克隆抗体(抗 HMGB1 mAb)可保留病变区域并改善运动恢复。为了进一步提高恢复,我们在这里检查了抗 HMGB1 mAb 和埃坡霉素 B (Epo B) 的组合治疗,据报道其可促进轴突再生。与单独的抗 HMGB1 mAb 相比,这种组合治疗显着增加了后肢运动,尽管单独的 Epo B 未能增加功能恢复。这些结果与单独使用抗 HMGB1 mAb 能够减少病变区域扩散并增加病变周围存活的神经元数量一致,而 Epo B 仅与抗 HMGB1 mAb 结合促进轴突生长,表明抗 HMGB1 mAb 依赖性组织保存对于 Epo B 显示其治疗效果是必要的。综上所述,组合治疗可被视为 SCI 的一种新颖且临床适用的策略。

更新日期:2021-04-18
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