ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Astrocytes Are Primed by Chronic Neurodegeneration to Produce Exaggerated Chemokine and Cell Infiltration Responses to Acute Stimulation with the Cytokines IL-1β and TNF-α.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- Astrocyte store-operated calcium entry is required for centrally mediated neuropathic pain.Pain reports · 2026Article
- Epigenetic mechanisms of inflammatory memory in the central nervous system.Nature immunology · 2026Review
- The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?Journal of neuroinflammation · 2026Review
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- Neuroinflammation-induced downregulation of RAB7 in murine astrocytes disrupts endo-lysosomal homeostasis and induces astrogliosis.Cell communication and signaling : CCS · 2026Article
- Microglia-Astrocyte Cooperation and Peripheral T Cells in Alzheimer's Disease: State-of-the-Art and Treatment Perspectives.International journal of molecular sciences · 2026Review
- Anti-Inflammatory and Antioxidant Effects of ω-3 Polyunsaturated Fatty Acids on Astrocytes and Their Implications for the Blood-Brain Barrier's Integrity and Function.International journal of molecular sciences · 2026Review
- Inflammatory microglia signals drive A1-like polarization of astrocytes even in the presence of HIV-1 Tat.Molecular neurobiology · 2025Article
- Redox-Immune Axis and Ozone Pollution: From Oxidative Stress to Thymic Involution and Neurodegeneration.Medical sciences (Basel, Switzerland) · 2025Review
- Microglia-astrocyte crosstalk following ischemic stroke.Molecular brain · 2025Review
- Evaluating the Neuroprotective Effects of Levetiracetam on Experimental Sciatic Nerve Injury.Journal of clinical medicine · 2025Article
- Neutrophils-astrocyte interactions in central nervous system inflammation.Cell death & disease · 2025Review
- Heterogeneity of Astrocyte Reactivity.Annual review of neuroscience · 2025Review
- Delirium pathophysiology in cancer: neurofilament light chain biomarker - narrative review.BMJ supportive & palliative care · 2025Review
- Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.Annals of neurology · 2025Article
- The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms.Journal of neuroinflammation · 2025Review
- Preventive effects of perioperative drug injection on postoperative delirium after hip fracture surgery: a systematic review and meta-analysis.American journal of translational research · 2025Review
- Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV.Frontiers in immunology · 2025Article
- Extracellular Vesicle MicroRNAs as Predictive Biomarkers in Postoperative Delirium After Spine Surgery: Preliminary Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Microgliosis and astrogliosis are standard pathological features of neurodegenerative disease. Microglia are primed by chronic neurodegeneration such that toll-like receptor agonists, such as LPS, drive exaggerated cytokine responses on this background. However, sterile inflammatory insults are more common than direct CNS infection in the degenerating brain and these insults drive robust IL-1β and TNF-α responses. It is unclear whether these pro-inflammatory cytokines can directly induce exaggerated responses in the degenerating brain. We hypothesized that glial cells in the hippocampus of animals with chronic neurodegenerative disease (ME7 prion disease) would display exaggerated responses to central cytokine challenges. TNF-α or IL-1β were administered intrahippocampally to ME7-inoculated mice and normal brain homogenate-injected (NBH) controls. Both IL-1β and TNF-α produced much more robust IL-1β synthesis in ME7 than in NBH animals and this occurred exclusively in microglia. However, there was strong nuclear localization of the NFκB subunit p65 in the astrocyte population, associated with marked astrocytic synthesis of the chemokines CXCL1 and CCL2 in response to both cytokine challenges in ME7 animals. Conversely, very limited expression of these chemokines was apparent in NBH animals similarly challenged. Thus, astrocytes are primed in the degenerating brain to produce exaggerated chemokine responses to acute stimulation with pro-inflammatory cytokines. Furthermore, this results in markedly increased neutrophil, T-cell, and monocyte infiltration in the diseased brain. These data have significant implications for acute sterile inflammatory insults such as stroke and traumatic brain injury occurring on a background of aging or neurodegeneration.
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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.