ArticleJournal of neurochemistry2012
Hypoxic preconditioning induces stroke tolerance in mice via a cascading HIF, sphingosine kinase, and CCL2 signaling pathway.
Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
- Hypoxic Preconditioning: An Underestimated Endogenous Protective Strategy?Biomolecules · 2026Review
- The Role of Sphingosine-1-Phosphate Signaling in Cerebral Ischemia/Reperfusion Injury and Alzheimer's Disease Pathology.International journal of molecular sciences · 2026Review
- Sphingosine Kinase 2 Inhibition Ameliorates Neuroinflammation in Diet-Induced Obese Mice.Aging and disease · 2025Article
- The Role of Hyperbaric Oxygen Therapy in Neuroregeneration and Neuroprotection: A Review.Cureus · 2024Review
- Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Intermittent hypoxia conditioning as a potential prevention and treatment strategy for ischemic stroke: Current evidence and future directions.Frontiers in neuroscience · 2022Review
- Article
- Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia in Subarachnoid Hemorrhage in Response to Hypoxic Postconditioning.Journal of the American Heart Association · 2021Article
- Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts.American journal of physiology. Heart and circulatory physiology · 2021Article
- Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling.International journal of molecular sciences · 2021Review
- Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia.International journal of molecular sciences · 2021Review
- Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment.Neuromolecular medicine · 2021Review
- Sphingosine 1-Phosphate Receptors in Cerebral Ischemia.Neuromolecular medicine · 2021Review
- A Rationale for Hypoxic and Chemical Conditioning in Huntington's Disease.International journal of molecular sciences · 2021Review
- Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke.Frontiers in neurology · 2021Article
- Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish.Molecular neurobiology · 2020Article
- Review
- Enhancing the Therapeutic Potential ofInternational journal of molecular sciences · 2020Article
- Neuroprotective Effect of HIF Prolyl Hydroxylase Inhibition in an In Vitro Hypoxia Model.Antioxidants (Basel, Switzerland) · 2020Article
- The S1P-S1PR Axis in Neurological Disorders-Insights into Current and Future Therapeutic Perspectives.Cells · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The induction of ischemic tolerance by preconditioning provides a platform to elucidate endogenous mechanisms of stroke protection. In these studies, we characterize the relationship between hypoxia-inducible factor (HIF), sphingosine kinase 2 (SphK2), and chemokine (C-C motif) ligand 2 (CCL2) in models of hypoxic or pharmacological preconditioning-induced ischemic tolerance. A genetics-based approach using SphK2- and CCL2-null mice showed both SphK2 and CCL2 to be necessary for the induction of ischemic tolerance following preconditioning with hypoxia, the hypoxia-mimetic cobalt chloride, or the sphingosine-1-phosphate (S1P) agonist FTY720. A pharmacological approach confirmed the necessity of HIF signaling for all three preconditioning stimuli, and showed that the SphK/S1P pathway transduces tolerance via the S1P(1) receptor. In addition, our data suggest significant cross-talk between HIF and SphK2-produced S1P signaling, which together act to up-regulate CCL2 expression. Overall, HIF, SphK, S1P, and CCL2 participate in a signaling cascade to induce the gene expression responsible for the stroke-tolerant phenotype established by hypoxic and FTY720 preconditioning. The identification of these common molecular mediators involved in signaling the genomic response to multiple preconditioning stimuli provides several targets for therapeutic manipulation.
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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.