ArticlePloS one2013
Decreased extracellular adenosine levels lead to loss of hypoxia-induced neuroprotection after repeated episodes of exposure to hypoxia.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Intracerebral microdialysis of adenosine and adenosine monophosphate - a systematic review and meta-regression analysis of baseline concentrations.Journal of neurochemistry · 2018Pooled it
- Structure-Activity Relationship Studies in a Series of Xanthine Inhibitors of SLACK Potassium Channels.Molecules (Basel, Switzerland) · 2024Article
- Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia.International journal of molecular sciences · 2024Review
- Hypoxia-adenosinergic regulation of B cell responses.Frontiers in immunology · 2024Review
- AInternational journal of molecular sciences · 2023Article
- Adenosine as a Key Mediator of Neuronal Survival in Cerebral Ischemic Injury.Neurochemical research · 2022Review
- A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality.iScience · 2022Article
- Spontaneous, transient adenosine release is not enhanced in the CA1 region of hippocampus during severe ischemia models.Journal of neurochemistry · 2021Article
- Article
- Neuropathic pain releasing calcitonin gene related peptide protects against stroke in rats.American journal of translational research · 2020Article
- Is there a central role for the cerebral endothelium and the vasculature in the brain response to conditioning stimuli?Conditioning medicine · 2018Article
- Regional Variations of Spontaneous, Transient Adenosine Release in Brain Slices.ACS chemical neuroscience · 2018Article
- Adenosine APurinergic signalling · 2016Article
- The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS.Brain sciences · 2016Review
- Mdivi-1 Protects Against Ischemic Brain Injury via Elevating Extracellular Adenosine in a cAMP/CREB-CD39-Dependent Manner.Molecular neurobiology · 2016Article
- Real-time monitoring of extracellular adenosine using enzyme-linked microelectrode arrays.Biosensors & bioelectronics · 2015Article
- Quantification of neurovascular protection following repetitive hypoxic preconditioning and transient middle cerebral artery occlusion in mice.Journal of visualized experiments : JoVE · 2015Article
- Extending injury- and disease-resistant CNS phenotypes by repetitive epigenetic conditioning.Frontiers in neurology · 2015Review
- Non-pharmaceutical therapies for stroke: mechanisms and clinical implications.Progress in neurobiology · 2014Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Achieving a prolonged neuroprotective state following transient ischemic attacks (TIAs) is likely to effectively reduce the brain damage and neurological dysfunction associated with recurrent stroke. HPC is a phenomenon in which advanced exposure to mild hypoxia reduces the stroke volume produced by a subsequent TIA. However, this neuroprotection is not long-lasting, with the effects reaching a peak after 3 days. Therefore, in this study, we investigated the use of multiple episodes of hypoxic exposure at different time intervals to induce longer-term protection in a mouse stroke model. C57BL/6 mice were subjected to different hypoxic preconditioning protocols: a single episode of HPC or five identical episodes at intervals of 3 days (E3d HPC) or 6 days (E6d HPC). Three days after the last hypoxic exposure, temporary middle cerebral artery occlusion (MCAO) was induced. The effects of these HPC protocols on hypoxia-inducible factor (HIF) regulated gene mRNA expression were measured by quantitative PCR. Changes in extracellular adenosine concentrations, known to exert neuroprotective effects, were also measured using in vivo microdialysis and high pressure liquid chromatography (HPLC). Neuroprotection was provided by E6d HPC but not E3d HPC. HIF-regulated target gene expression increased significantly following all HPC protocols. However, E3d HPC significantly decreased extracellular adenosine and reduced cerebral blood flow in the ischemic region with upregulated expression of the adenosine transporter, equilibrative nucleoside transporter 1 (ENT1). An ENT1 inhibitor, propentofylline increased the cerebral blood flow and re-established neuroprotection in E3d HPC. Adenosine receptor specific antagonists showed that adenosine mainly through A1 receptor mediates HPC induced neuroprotection. Our data indicate that cooperation of HIF-regulated genes and extracellular adenosine is necessary for HPC-induced neuroprotection.
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