Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection afte
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RESEARCH
Open Access
Inhibiting HMGB1-RAGE axis prevents proinflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury Hong Fan1,2†, Hai-Bin Tang3†, Zhe Chen4†, Hu-Qing Wang1, Lei Zhang1, Yu Jiang1, Tao Li1, Cai-Feng Yang4, Xiao-Ya Wang1, Xia Li5, Sheng-Xi Wu2* and Gui-Lian Zhang1*
Abstract Background: Spinal cord injury (SCI) favors a persistent pro-inflammatory macrophages/microglia-mediated response with only a transient appearance of anti-inflammatory phenotype of immune cells. However, the mechanisms controlling this special sterile inflammation after SCI are still not fully elucidated. It is known that damage-associated molecular patterns (DAMPs) released from necrotic cells after injury can trigger severe inflammation. High mobility group box 1(HMGB1), a ubiquitously expressed DNA binding protein, is an identified DAMP, and our previous study demonstrated that reactive astrocytes could undergo necroptosis and release HMGB1 after SCI in mice. The present study aimed to explore the effects and the possible mechanism of HMGB1on macrophages/microglia polarization, as well as the neuroprotective effects by HMGB1 inhibition after SCI. Methods: In this study, the expression and the concentration of HMGB1 was determined by qRT-PCR, ELISA, and immunohistochemistry. Glycyrrhizin was applied to inhibit HMGB1, while FPS-ZM1 to suppress receptor for advanced glycation end products (RAGE). The polarization of macrophages/microglia in vitro and in vivo was detected by qRT-PCR, immunostaining, and western blot. The lesion area was detected by GFAP staining, while neuronal survival was examined by Nissl staining. Luxol fast blue (LFB) staining, DAB staining, and western blot were adopted to evaluate the myelin loss. Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay was applied to evaluate locomotor functional recovery. (Continued on next page)
* Correspondence: [email protected]; [email protected] † Hong Fan, Hai-Bin Tang and Zhe Chen contributed equally to this work. 2 Institute of Neurosciences, Fourth Military Medical University, Xi’an 710032, Shaanxi, China 1 Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you w
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