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• W2013260733 abstract "Protection of the blood–brain barrier (BBB) is correlated with improved outcome in stroke. Sphingosine kinase (SphK)-directed production of sphingosine-1-phosphate, which we previously documented as being vital to preconditioning-induced stroke protection, mediates peripheral vascular integrity via junctional protein regulation. We used a hypoxic preconditioning (HPC) model in adult wild-type and SphK2-null mice to examine the isoform-specific role of SphK2 signaling for ischemic tolerance to transient middle cerebral artery occlusion and attendant BBB protection. Reductions in infarct volume and BBB permeability in HPC-treated mice were completely lost in SphK2-null mice. Hypoxic preconditioning-induced attenuation of postischemic BBB disruption in wild types, evidenced by reduced extravascular immunoglobulin G intensity, suggests direct protection of BBB integrity. Measurement of BBB junctional protein status in response to HPC revealed SphK2-dependent increases in triton-insoluble claudin-5 and VE-cadherin, which may serve to strengthen the BBB before stroke. Postischemic loss of VE-cadherin, occludin, and zona occludens-1 in SphK2-null mice with prior HPC suggests that SphK2-dependent protection of these adherens and tight junction proteins is compulsory for HPC to establish a vasculoprotective phenotype. Further elucidation of the mediators of this endogenous, HPC-activated lipid signaling pathway, and their role in protecting the ischemic BBB, may provide new therapeutic targets for cerebrovascular protection in stroke patients." @default.
• W2013260733 created "2016-06-24" @default.
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• W2013260733 date "2012-02-08" @default.
• W2013260733 modified "2023-10-16" @default.
• W2013260733 title "Junctional Protein Regulation by Sphingosine Kinase 2 Contributes to Blood–Brain Barrier Protection in Hypoxic Preconditioning-Induced Cerebral Ischemic Tolerance" @default.
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• W2013260733 doi "https://doi.org/10.1038/jcbfm.2012.3" @default.
• W2013260733 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3367228" @default.
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