ArticleJournal of neuroinflammation2021
AXL kinase-mediated astrocytic phagocytosis modulates outcomes of traumatic brain injury.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- MERTK-related engulfment of norepinephrinergic neuronal presynaptic membrane by astrocytes following acute TBI and potentiation effect of peripheral nerve modulation.Annals of medicine · 2026Article
- Integrated analysis of single-cell and transcriptome data reveals temporal dynamics of microglial phagocytic reprogramming in neuropathic pain progression.Scientific reports · 2026Article
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- 3D-bioprinted adipose-derived stem cell-secreted GAS6Journal of nanobiotechnology · 2026Article
- TRIM21 Exacerbates Ischemic Brain Injury by Promoting Astrocyte-Mediated Neuroinflammation via K63-Linked Ubiquitination of MDA5.Research (Washington, D.C.) · 2026Article
- Astrocytic SIRT1 ameliorates cognitive deficits after traumatic brain injury via autophagy-mediated MEGF10 phagocytosis.Journal of neuroinflammation · 2025Article
- Human oligodendrocyte progenitor cells mediate synapse elimination through TAM receptor activation.Nature communications · 2025Article
- Impaired Efferocytosis of Pericytes and Vascular Smooth Muscle Cells in Diabetic Retinopathy.Cells · 2025Review
- Impaired microglial glycolysis promotes inflammatory responses after intracerebral haemorrhage via HK2-dependent mitochondrial dysfunction.Journal of advanced research · 2025Article
- Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD.Communications biology · 2025Article
- Selective regulation of corticostriatal synapses by astrocytic phagocytosis.Nature communications · 2025Article
- Aquaporin‑1 regulates microglial polarization and inflammatory response in traumatic brain injury.International journal of molecular medicine · 2025Article
- Immunomodulatory effect of efferocytosis at the maternal-fetal interface.Cell communication and signaling : CCS · 2025Review
- The roles of microglia and astrocytes in neuroinflammation of Alzheimer's disease.Frontiers in neuroscience · 2025Review
- Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke.Stroke and vascular neurology · 2024Article
- Passive immunotherapy for Alzheimer's disease: challenges & future directions.Journal of translational medicine · 2024Review
- Article
- Neutrophil-like pH-responsive pro-efferocytic nanoparticles improve neurological recovery by promoting erythrophagocytosis after intracerebral hemorrhage.Theranostics · 2024Article
- Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice.Translational stroke research · 2023Article
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Authors and funding
20 authors at 2 institutions in 1 country.
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Abstract
backgroundComplex changes in the brain microenvironment following traumatic brain injury (TBI) can cause neurological impairments for which there are few efficacious therapeutic interventions. The reactivity of astrocytes is one of the keys to microenvironmental changes, such as neuroinflammation, but its role and the molecular mechanisms that underpin it remain unclear.
methodsMale C57BL/6J mice were subjected to the controlled cortical impact (CCI) to develop a TBI model. The specific ligand of AXL receptor tyrosine kinase (AXL), recombinant mouse growth arrest-specific 6 (rmGas6) was intracerebroventricularly administered, and selective AXL antagonist R428 was intraperitoneally applied at 30 min post-modeling separately. Post-TBI assessments included neurobehavioral assessments, transmission electron microscopy, immunohistochemistry, and western blotting. Real-time polymerase chain reaction (RT-PCR), siRNA transfection, and flow cytometry were performed for mechanism assessments in primary cultured astrocytes.
resultsAXL is upregulated mainly in astrocytes after TBI and promotes astrocytes switching to a phenotype that exhibits the capability of ingesting degenerated neurons or debris. As a result, this astrocytic transformation promotes the limitation of neuroinflammation and recovery of neurological dysfunction. Pharmacological inhibition of AXL in astrocytes significantly decreased astrocytic phagocytosis both in vivo and in primary astrocyte cultures, in contrast to the effect of treatment with the rmGas6. AXL activates the signal transducer and activator of the transcription 1 (STAT1) pathway thereby further upregulating ATP-binding cassette transporter 1 (ABCA1). Moreover, the supernatant from GAS6-depleted BV2 cells induced limited enhancement of astrocytic phagocytosis in vitro.
conclusionOur work establishes the role of AXL in the transformation of astrocytes to a phagocytic phenotype via the AXL/STAT1/ABCA1 pathway which contributes to the separation of healthy brain tissue from injury-induced cell debris, further ameliorating neuroinflammation and neurological impairments after TBI. Collectively, our findings provide a potential therapeutic target for TBI.
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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.