ArticleJournal of neuroinflammation2020
Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 5 of them syntheses that pooled it.
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Who cites it
152 citing papers in PubMed, 5 syntheses or guidelines pooled it, 265 citations in OpenAlex.
- Immunoregulation of Glia after spinal cord injury: a bibliometric analysis.Frontiers in immunology · 2024Pooled it
- Stem Cell Strategies in Promoting Neuronal Regeneration after Spinal Cord Injury: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- The Anti-inflammation Property of Olfactory Ensheathing Cells in Neural Regeneration After Spinal Cord Injury.Molecular neurobiology · 2022Pooled it
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- Therapeutic effects and long-term outcomes of HMGB1-targeted therapy in rats and mice with traumatic spinal cord injury: A systematic review and meta-analysis.Frontiers in neuroscience · 2022Pooled it
- High mobility group box 1 and its post-translational modifications: Molecular mechanisms underlying neurodegenerative disease pathogenesis.Neural regeneration research · 2026Article
- Cell death in ischemia-reperfusion injury: beyond a single-cell-death perspective.Biomarker research · 2026Review
- Oleuropein Reduces Secondary Injury Pathways After Experimental Spinal Cord Injury Via HMGB1-Associated Signaling.Medeniyet medical journal · 2026Article
- 3-Hydroxydehydroleucodin ameliorates neuroinflammation and ischemic brain injury by blocking the TRIM21-PRDX1 interaction.Acta pharmacologica Sinica · 2026Article
- Emodin Suppresses the RAGE/ROCK1 Pathway to Modulate the Oligodendrocyte Lineage and Ameliorate Demyelination in Vascular Dementia Rats.CNS neuroscience & therapeutics · 2026Article
- M2 polarization of macrophages: Manipulation of spinal cord injury repair.Neural regeneration research · 2026Article
- Astragaloside IV mitigates mitochondrial damage and neurological symptoms in rats with cervical spondylotic myelopathy by inhibiting IL-17/TRAF6/NF-κB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Protein-protein interaction-mediated signaling networks in ischemic stroke: from molecular mechanisms to therapeutic strategies.Acta pharmacologica Sinica · 2026Review
- Exacerbation of neuronal senescence after spinal cord injury: Role of the macrophage-derived transforming growth factor-β1-SMAD2 signaling axis.Neural regeneration research · 2026Article
- Structural and molecular principles of DAMP biology.Nature structural & molecular biology · 2026Review
- HMGB1 impairs nasal epithelial barrier via regulating autophagy in the pathogenesis of allergic rhinitis.The World Allergy Organization journal · 2026Article
- Recombinant Artemin-Fc Fusion Protein Attenuates TLR4/NF-κB-Associated Neuroinflammation and Modulates Inhibitory/Excitatory Synaptic Marker Expression After Spinal Cord Injury.CNS neuroscience & therapeutics · 2026Article
- The Pleiotropic Therapeutic Perspectives of GLP-1 and GIP Receptor Agonists in Spinal Cord Injury: A Narrative Review.Molecular neurobiology · 2026Review
- PBAE nanoparticle-mediated delivery of ASCL1 and NGN2 genes for astroglia-to-neuron reprogramming to remodel glial scar for spinal cord injury repair.Stem cell research & therapy · 2026Article
- Electroacupuncture-modulated DHCR24 facilitates spinal cord injury recovery by attenuating apoptosis and neuroinflammation via the Wnt signaling pathway.Metabolic brain disease · 2026Article
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSpinal 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.
methodsIn 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.
resultsOur data showed that HMGB1 can be elevated and released from necroptotic astrocytes and HMGB1 could induce pro-inflammatory microglia through the RAGE-nuclear factor-kappa B (NF-κB) pathway. We further demonstrated that inhibiting HMGB1 or RAGE effectively decreased the numbers of detrimental pro-inflammatory macrophages/microglia while increased anti-inflammatory cells after SCI. Furthermore, our data showed that inhibiting HMGB1 or RAGE significantly decreased neuronal loss and demyelination, and improved functional recovery after SCI.
conclusionsThe data implicated that HMGB1-RAGE axis contributed to the dominant pro-inflammatory macrophages/microglia-mediated pro-inflammatory response, and inhibiting this pathway afforded neuroprotection for SCI. Thus, therapies designed to modulate immune microenvironment based on this cascade might be a prospective treatment for SCI.
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