ArticleMolecular neurodegeneration2016
Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 3 of them syntheses that pooled it.
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Who cites it
131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 234 citations in OpenAlex.
- Immunoregulation of Glia after spinal cord injury: a bibliometric analysis.Frontiers in immunology · 2024Pooled it
- Bibliometric and visual analysis of spinal cord injury-associated macrophages from 2002 to 2023.Frontiers in neurology · 2023Pooled it
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- Spatiotemporal disarray of inflammatory microenvironment following spinal cord injury.Neural regeneration research · 2026Article
- The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies.Neural regeneration research · 2026Article
- Hypoxia Upregulates RIPK1 via the HIF-1α-JAK-STAT Pathway Leading to Astrocyte Necroptosis to Promote Cavitation After Spinal Cord Injury.CNS neuroscience & therapeutics · 2026Article
- Multiomics Profiling Identifies Tlr4 as a Therapeutic Target of Necroptosis in Spinal Cord Injury.Mediators of inflammation · 2026Article
- Single-cell RNA-seq combined with bulk RNA-seq analysis identifies necroptosis-related genes as therapeutic targets for periodontitis.BMC medical genomics · 2025Article
- Neuroimmune, metabolic and oxidative stress pathways in major depressive disorder.Nature reviews. Neurology · 2025Review
- CircGTF2H2C Regulates NLRP3 Dephosphorylation via Modulating PTPN11 Expression in Spinal Cord Injury.Molecular neurobiology · 2025Article
- PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue.Microorganisms · 2025Article
- Effect of microglial Pd1 on glial scar formation after spinal cord injury in mice.The Journal of biological chemistry · 2025Article
- Microglia-Derived Interleukin-6 Triggers Astrocyte Apoptosis in the Hippocampus and Mediates Depression-Like Behavior.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MTOR Promotes Astrocyte Activation and Participates in Neuropathic Pain through an Upregulation of RIP3.Neurochemical research · 2025Article
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Mechanisms of Traumatic Spinal Cord Injury AIS Grade Conversion.Neurotrauma reports · 2025Review
- The emerging role of cuproptosis in spinal cord injury.Frontiers in immunology · 2025Review
- Activation of FANCC attenuates mitochondrial ROS-driven necroptosis by targeting TBK1-dependent mitophagy in astrocytes after spinal cord injury.Theranostics · 2025Article
- Exploring gut microbiota and spinal cord injury: pathogenesis, treatment strategies and prospects.Frontiers in immunology · 2025Review
- Role of necroptosis in pulpitis: integration of bacterial infection, immune imbalance, and oxidative stress.PeerJ · 2025Review
71 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA unique feature of the pathological change after spinal cord injury (SCI) is the progressive enlargement of lesion area, which usually results in cavity formation and is accompanied by reactive astrogliosis and chronic inflammation. Reactive astrocytes line the spinal cavity, walling off the lesion core from the normal spinal tissue, and are thought to play multiple important roles in SCI. The contribution of cell death, particularly the apoptosis of neurons and oligodendrocytes during the process of cavitation has been extensively studied. However, how reactive astrocytes are eliminated following SCI remains largely unclear.
resultsBy immunohistochemistry, in vivo propidium iodide (PI)-labeling and electron microscopic examination, here we reported that in mice, reactive astrocytes died by receptor-interacting protein 3 and mixed lineage kinase domain-like protein (RIP3/MLKL) mediated necroptosis, rather than apoptosis or autophagy. Inhibiting receptor-interacting protein 1 (RIP1) or depleting RIP3 not only significantly attenuated astrocyte death but also rescued the neurotrophic function of astrocytes. The astrocytic expression of necroptotic markers followed the polarization of M1 microglia/macrophages after SCI. Depleting M1 microglia/macrophages or transplantation of M1 macrophages could significantly reduce or increase the necroptosis of astrocytes. Further, the inflammatory responsive genes Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) are induced in necroptotic astrocytes. In vitro antagonizing MyD88 in astrocytes could significantly alleviate the M1 microglia/macrophages-induced cell death. Finally, our data showed that in human, necroptotic markers and TLR4/MyD88 were co-expressed in astrocytes of injured, but not normal spinal cord.
conclusionTaken together, these results reveal that after SCI, reactive astrocytes undergo M1 microglia/macrophages-induced necroptosis, partially through TLR/MyD88 signaling, and suggest that inhibiting astrocytic necroptosis may be beneficial for preventing secondary SCI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.