ArticleCNS neuroscience & therapeutics2021
Sphingosine-1-phosphate receptor 3 is implicated in BBB injury via the CCL2-CCR2 axis following acute intracerebral hemorrhage.
Article in CNS neuroscience & therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Irisin Restrains Oligodendroglial Ferroptosis to Preserve White Matter After Traumatic Brain Injury via AMPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Sphingosine-1-Phosphate Receptor 3 Mediated Neuroinflammation is Critically Involved in the Development of Brain Injury Following Cardiac Arrest in Mice.Neurochemical research · 2026Article
- G Protein-Coupled Receptors in Cerebrovascular Diseases: Signaling Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Sphingosine Kinase 2 Inhibition Ameliorates Neuroinflammation in Diet-Induced Obese Mice.Aging and disease · 2025Article
- Gut microbial metabolite, sphingosine-1-phosphate (S1P), drives mesangial cell phenotypic transformation and accelerates progression of IgA nephropathy via CCL2-MET-FAK pathway.Current research in microbial sciences · 2025Article
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- Sphk1/S1P pathway promotes blood-brain barrier breakdown after intracerebral hemorrhage through inducing Nlrp3-mediated endothelial cell pyroptosis.Cell death & disease · 2024Article
- Silencing CXCL16 alleviate neuroinflammation and M1 microglial polarization in mouse brain hemorrhage model and BV2 cell model through PI3K/AKT pathway.Experimental brain research · 2024Article
- A2 reactive astrocyte-derived exosomes alleviate cerebral ischemia-reperfusion injury by delivering miR-628.Journal of cellular and molecular medicine · 2024Article
- Immune-mediated disruption of the blood-brain barrier after intracerebral hemorrhage: Insights and potential therapeutic targets.CNS neuroscience & therapeutics · 2024Review
- Article
- Prediction of post-stroke depression with combined blood biomarkers IL-6, TNF-a, and fatty acid binding protein: A prospective study.Journal of medical biochemistry · 2023Article
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Sphingosine 1-phosphate receptor 1 regulates blood-brain barrier permeability in epileptic mice.Neural regeneration research · 2023Article
- The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery.Biomolecules · 2023Review
- Adipokines in atherosclerosis: unraveling complex roles.Frontiers in cardiovascular medicine · 2023Review
- Decreased Astrocytic CCL2 Accounts for BAF-312 Effect on PBMCs Transendothelial Migration Through a Blood Brain Barrier in Vitro Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- ANAID-ICH nomogram for predicting unfavorable outcome after intracerebral hemorrhage.CNS neuroscience & therapeutics · 2022Article
- An Update on Sphingosine-1-Phosphate and Lysophosphatidic Acid Receptor Transcripts in Rodent Olfactory Mucosa.International journal of molecular sciences · 2022Article
- The Role of CCL2/CCR2 Axis in Cerebral Ischemia-Reperfusion Injury and Treatment: From Animal Experiments to Clinical Trials.International journal of molecular sciences · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntracerebral hemorrhage (ICH) is a catastrophic cerebrovascular disease with high morbidity and mortality. Evidence demonstrated that sphingosine-1-phosphate receptor (S1PR) plays a vital role in inflammatory damage via the upregulation of CCL2 expression. However, whether S1PR3 is involved in blood-brain barrier (BBB) breakdown via CCL2 activation after ICH has not been described.
methodsWe investigated the expression profiles of all S1PRs using high-throughput RNA-seq analysis and RT-PCR. The potential role of S1PR3 and interaction between S1PR3 and CCL2 were evaluated via Western blotting, immunofluorescence, and flow cytometry. BBB disruption was examined via magnetic resonance imaging, transmission electron microscopy, and Evans blue extravasation. Microglial activation, proliferation, and polarization were assessed via histopathological analysis. The expression levels of CCL2, p-p38 MAPK, ICAM-1, and ZO-1 were examined in vitro and in vivo.
resultsThe present results showed that the levels of S1PR3 and its ligand, sphingosine 1-phosphate (S1P), were dramatically increased following ICH, which regulated the expression of CCL2 and p38MAPK. Moreover, reductions in brain edema volume, amelioration of BBB integrity, and improvements in behavioral deficits were achieved after the administration of CAY10444, an S1PR3 antagonist, to rats. Remarkably increased CCL2, p-p38MAPK, and ICAM-1 expression and decreased ZO-1 expression were observed in cocultured human astrocytes (HAs) and hCMEC/D3 cells after S1P stimulation. However, the expression levels of CCL2, p-p38 MAPK, and ICAM-1 were decreased and ZO-1 expression was increased after S1PR3 inhibition. In addition, microglial proliferation and M1 polarization were attenuated after CAY10444 administration.
conclusionTo the best of our knowledge, this is the first demonstration of the neuroprotective role of S1PR3 modulation in maintaining BBB integrity by inhibiting the S1PR3-CCL2 axis after ICH, providing a novel treatment for ICH by targeting S1PR3.
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