ArticleScientific reports2016
Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- The Role of Tumor Necrosis Factor Following Spinal Cord Injury: A Systematic Review.Cellular and molecular neurobiology · 2023Pooled it
- The Role of TNF-α in Ischemic Stroke.International journal of molecular sciences · 2026Review
- Ischemic stroke neuroprotection revisited: translational barriers and a phase-resolved, biomarker-anchored framework.Archives of pharmacal research · 2026Review
- The gut-brain axis: mechanisms linking intestinal dysbiosis with stroke.Frontiers in cell and developmental biology · 2026Review
- TNFR2 signaling shapes the sex-specific remyelinating properties of microglia after experimental stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Systemic inhibition of soluble TNF significantly changes glial cell populations leading to improved myelin integrity and better functional outcome after experimental stroke.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Microglial TNFR2 signaling regulates the inflammatory response after CNS injury in a sex-specific fashion.Brain, behavior, and immunity · 2024Article
- USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Crosstalk Between Autophagy and Inflammation in Chronic Cerebral Ischaemia.Cellular and molecular neurobiology · 2023Review
- Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization.PLoS biology · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Inflammatory biomarkers of ischemic stroke.Internal and emergency medicine · 2023Review
- Inflammatory Responses After Ischemic Stroke.Seminars in immunopathology · 2022Review
- Review
- Microglial re-modeling contributes to recovery from ischemic injury of rat brain: A study using a cytokine mixture containing granulocyte-macrophage colony-stimulating factor and interleukin-3.Frontiers in neuroscience · 2022Article
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- Article
- Cytokines as therapeutic targets for cardio- and cerebrovascular diseases.Basic research in cardiology · 2021Review
- Cooling and Sterile Inflammation in an Oxygen-Glucose-Deprivation/Reperfusion Injury Model in BV-2 Microglia.Mediators of inflammation · 2021Article
- Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Microglia are activated following cerebral ischemia and increase their production of the neuro- and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNF(fl/fl)) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide-stimulated cultured primary microglia by ~93%. Furthermore, phosphorylated-ERK/ERK ratios were significantly decreased in naïve LysMcreTNF(fl/fl) mice demonstrating altered ERK signal transduction. Micro-PET using (18)[F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNF(fl/fl) mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naïve LysMcreTNF(fl/fl) mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNF(fl/fl) mice compared to littermate mice, whereas no TNF(+) leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL-1β, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNF(fl/fl) mice, despite comparable infiltrating leukocyte populations. Our results identify microglial TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery.
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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.