Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury. (November 2021)

• Record Type: Journal Article
• Authors: Zhu, Yicheng; Uezono, Naohiro; Yasui, Tetsuro; Nakajo, Masahide; Nagai, Tatsuya; Wang, Dengli; Nishibori, Masahiro; Nakashima, Kinichi
• Is Part Of: Neuroscience research. Volume 172(2021)
• Page Start: 13
• Page End: 25
• Publication Date: 2021-11
• Subjects: SCI spinal cord injury -- HMGB1 High Mobility Group Box-1 -- mAb monoclonal antibody -- Epo B epothilone B -- CNS central nervous system -- TLR toll-like receptor -- BBB blood brain barrier -- BSCB blood-spinal cord barrier -- RRID Research Resource Identifiers -- hiPSC-NSCs human induced pluripotent stem cells-derived neural stem cells -- BW body weight -- BMS Basso Mouse Scale -- PBS phosphate buffered saline -- GFAP glial fibrillary acidic protein -- 5-HT 5-hydroxytryptamine -- RST raphespinal tract -- i.p. intraperitoneal -- CST corticospinal tract -- ChAT Choline acetyltransferase -- TNF-α tumor necrosis factor α; Spinal cord injury -- Contusion injury -- High Mobility Group Box-1 -- Epothilone B -- Functional recovery -- Axon regeneration; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2021.04.002
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: 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. Abstract: 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.