ArticleNature communications2022
Reactive astrocytes transduce inflammation in a blood-brain barrier model through a TNF-STAT3 signaling axis and secretion of alpha 1-antichymotrypsin.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Integrated meta-analysis of human astrocytes transcriptomes reveals a candidate recurrent inflammatory signature in response to inflammatory and immune stimuli.Frontiers in cellular neuroscience · 2026Pooled it
- A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.Molecular psychiatry · 2025Pooled it
- Article
- Injury-transduced oligodendrocytes modulate neuroinflammation and glial activation in diseased and non-diseased central nervous system.Nature communications · 2026Article
- Soluble TREM2 Mediates Blood Brain Barrier Permeability through Astrocyte Reactivity.Research square · 2026Article
- Serum SERPINA3 as a Candidate Non-Invasive Biomarker for Neuromyelitis Optica Spectrum Disorder: Proteomic Discovery and Same-Center Validation.Diagnostics (Basel, Switzerland) · 2026Article
- Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.Acta neuropathologica · 2026Review
- Ophthalmic and psychiatric health: the overlooked connection between ocular diseases and mental disorders.Eye (London, England) · 2026Review
- Transcriptomic analysis reveals that neural stem cell-derived exosomes regulate the HMGB1/TLR2 signaling axis to promote astrocytic differentiation and mitochondrial biogenesis in the repair of radiation-induced blood-brain barrier damage.Cell death discovery · 2026Article
- Targeting astrocytic Dp71 attenuates BBB disruption after traumatic brain injury through WTAP-associated mScience advances · 2026Article
- A Long-Lived Human Neurovascular PENTA Culture Model Captures Incomplete Vascular Repair and Glia-Associated Signaling After Traumatic Brain Injury.Advanced healthcare materials · 2026Article
- Myd88 Deficiency Accelerates Retinal Degeneration and Alters Microglial Dynamics in a Mouse Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Review
- Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Total flavones of Rhododendron protect against BBB injury following cerebral ischemia/reperfusion via promoting astrocytic polarization towards A2 subtype.Apoptosis : an international journal on programmed cell death · 2026Article
- Escherichia coli Nissle 1917 alleviates Alzheimer's disease in mice through OmpA-containing outer membrane vesicles.Cell reports. Medicine · 2026Article
- Responsive nanoparticles modulating microglia lactate transport alleviate M1-type polarization and neuroinflammation for brain injury therapy.Journal of nanobiotechnology · 2026Article
- Chloride Homeostasis Failure in Human Disease: KCC2/NKCC1 Microdomain Dysfunction as a Driver of Cortical Network Collapse.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
- Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Astrocytes are critical components of the neurovascular unit that support blood-brain barrier (BBB) function. Pathological transformation of astrocytes to reactive states can be protective or harmful to BBB function. Here, using a human induced pluripotent stem cell (iPSC)-derived BBB co-culture model, we show that tumor necrosis factor (TNF) transitions astrocytes to an inflammatory reactive state that causes BBB dysfunction through activation of STAT3 and increased expression of SERPINA3, which encodes alpha 1-antichymotrypsin (α1ACT). To contextualize these findings, we correlated astrocytic STAT3 activation to vascular inflammation in postmortem human tissue. Further, in murine brain organotypic cultures, astrocyte-specific silencing of Serpina3n reduced vascular inflammation after TNF challenge. Last, treatment with recombinant Serpina3n in both ex vivo explant cultures and in vivo was sufficient to induce BBB dysfunction-related molecular changes. Overall, our results define the TNF-STAT3-α1ACT signaling axis as a driver of an inflammatory reactive astrocyte signature that contributes to BBB dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.