ArticleMolecular neurobiology2020
Sphingosine 1-Phosphate Signaling Is Involved in Impaired Blood-Brain Barrier Function in Ischemia-Reperfusion Injury.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Several Common Genetic Variations Associate With Functional or Anatomic Effects of Anti-VEGF Treatment in Conditions With Macular Edema.Investigative ophthalmology & visual science · 2025Pooled it
- Danhong Injection Alleviates Blood-Brain Barrier Disruption Caused by Cerebral Ischemia-Reperfusion Injury inPharmaceuticals (Basel, Switzerland) · 2026Article
- Blocking S1PJournal of advanced research · 2025Article
- Serum sphingosine-1-phosphate levels are associated with brain metastasis inFuture oncology (London, England) · 2025Article
- Immunological Mechanisms and Therapeutic Strategies in Cerebral Ischemia-Reperfusion Injury: From Inflammatory Response to Neurorepair.International journal of molecular sciences · 2025Review
- RBM10 deficiency promotes brain metastasis by modulating sphingolipid metabolism in a BBB model of EGFR mutant lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood-brain barrier function in neurological diseases.Frontiers in neuroscience · 2025Review
- Sphk1/S1P pathway promotes blood-brain barrier breakdown after intracerebral hemorrhage through inducing Nlrp3-mediated endothelial cell pyroptosis.Cell death & disease · 2024Article
- Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate.iScience · 2024Article
- The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.The Journal of pharmacology and experimental therapeutics · 2024Review
- Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model.International journal of molecular sciences · 2022Article
- P-Glycoprotein Aggravates Blood Brain Barrier Dysfunction in Experimental Ischemic Stroke by Inhibiting Endothelial Autophagy.Aging and disease · 2022Article
- Protective Effects of Nuciferine in Middle Cerebral Artery Occlusion Rats Based on Transcriptomics.Brain sciences · 2022Article
- The Role of Sphingomyelin Metabolism in the Protection of Rat Brain Microvascular Endothelial Cells by Mild Hypothermia.Neurocritical care · 2022Article
- Histone methyltransferase Smyd2 contributes to blood-brain barrier breakdown in stroke.Clinical and translational medicine · 2022Article
- Defective Function of the Blood-Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model.Cellular and molecular neurobiology · 2022Article
- Long Non Coding RNA Based Regulation of Cerebrovascular Endothelium.Frontiers in genetics · 2022Review
- Sphingolipid metabolism and signaling in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- AIM2 deletion enhances blood-brain barrier integrity in experimental ischemic stroke.CNS neuroscience & therapeutics · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Sphingosine 1-phosphate (S1P) is a major bioactive lipid mediator in the vascular and immune system. Here, we have shown that inhibition of S1P signaling prevents blood-brain barrier (BBB) dysfunction after ischemia both in vitro and in vivo. In the in vitro BBB models, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of an S1P synthesizing enzyme (Sphk1) and S1P transporters (Abca1, Spns2), increasing S1P in culture media. Inhibitors of Sphk1 (SKI-II) or Abca1 (probucol) attenuated the decrease in transendothelial electrical resistance and the increase in permeability caused by OGD/R. In the middle cerebral artery occlusion and reperfusion (MCAO/R) model of mice, probucol administration after MCAO operation reduced the infarction area and vascular leakage, preserving the integrity of tight junction proteins. Furthermore, MCAO/R caused activation of STAT3, a downstream mediator of S1P signaling, which was suppressed by postoperative probucol administration. Accordingly, S1P activated STAT3, both in cultured vascular endothelial cells and pericytes, and STAT3 signaling inhibitor (Stattic) protected BBB dysfunction in OGD/R-treated in vitro BBB models. These results suggest that inhibition of S1P signaling is a strategy to treat BBB impairment after cerebral ischemia and highlight the potential alternative use of probucol, a classical anti-hyperlipidemic drug, for emergency treatment of stroke.
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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.