ArticleNeurobiology of disease2016
Role of Hypoxia Inducible Factor 1 in Hyperglycemia-Exacerbated Blood-Brain Barrier Disruption in Ischemic Stroke.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- SRT1720-loaded exosome-mimetic nanovesicles promote mitophagy via SIRT1/PARKIN activation to ameliorate diabetic cerebral infarction in a preclinical rat model.International journal of pharmaceutics: X · 2026Article
- Hypoxia-inducible factor-1: A new neuroprotective agent for the treatment of hyperglycemia after stroke.Neural regeneration research · 2026Article
- Luteolin Improves BBB Integrity Following Ischemic Stroke Injury by Downregulating the Expression of LRP1 and MMP9.Phytotherapy research : PTR · 2026Article
- Novel mechanism of neuronal hypoxia response: HIF-1α/STOML2 mediated PINK1-dependent mitophagy activation against neuronal injury.Cell death discovery · 2026Article
- HIF-1α in ischemic stroke: context-dependent roles in ferroptosis and neurovascular repair.Frontiers in neurology · 2026Review
- Effects of three aerobic exercise protocols on acute glucose response and continuous glucose monitoring trends in patients with type 2 diabetes mellitus and stroke: a randomized controlled trial.BMC sports science, medicine & rehabilitation · 2025Article
- Sex- and age- differences in the expression of critical blood-brain barrier regulators: a physiological context.Biology of sex differences · 2025Article
- Review
- Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation.Frontiers in aging neuroscience · 2025Article
- The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke: a comprehensive review.Frontiers in neuroscience · 2024Review
- Molecular and neural roles of sodium-glucose cotransporter 2 inhibitors in alleviating neurocognitive impairment in diabetic mice.Psychopharmacology · 2023Article
- A review of stress-induced hyperglycaemia in the context of acute ischaemic stroke: Definition, underlying mechanisms, and the status of insulin therapy.Frontiers in neurology · 2023Review
- Single nucleotide variations in the development of diabetic foot ulcer: A narrative review.World journal of diabetes · 2022Review
- Review
- Hyperglycemia in acute ischemic stroke: physiopathological and therapeutic complexity.Neural regeneration research · 2022Review
- Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo.Fluids and barriers of the CNS · 2022Article
- In Vitro Models of the Human Blood-Brain Barrier Utilising Human Induced Pluripotent Stem Cells: Opportunities and Challenges.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome.Angiogenesis · 2021Article
- Endothelial Thioredoxin-Interacting Protein Depletion Reduces Hemorrhagic Transformation in Hyperglycemic Mice after Embolic Stroke and Thrombolytic Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke.Cellular and molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes is a major stroke risk factor and is associated with poor functional recovery after stroke. Accumulating evidence indicates that the worsened outcomes may be due to hyperglycemia-induced cerebral vascular complications, especially disruption of the blood-brain barrier (BBB). The present study tested a hypothesis that the activation of hypoxia inducible factor-1 (HIF-1) was involved in hyperglycemia-aggravated BBB disruption in an ischemic stroke model. Non-diabetic control and Streptozotocin-induced type I diabetic mice were subjected to 90min transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Our results demonstrated that hyperglycemia induced higher expression of HIF-1α and vascular endothelial growth factor (VEGF) in brain microvessels after MCAO/reperfusion. Diabetic mice showed exacerbated BBB damage and tight junction disruption, increased infarct volume as well as worsened neurological deficits. Furthermore, suppressing HIF-1 activity by specific knock-out endothelial HIF-1α ameliorated BBB leakage and brain infarction in diabetic animals. Moreover, glycemic control by insulin abolished HIF-1α up-regulation in diabetic animals and reduced BBB permeability and brain infarction. These findings strongly indicate that HIF-1 plays an important role in hyperglycemia-induced exacerbation of BBB disruption in ischemic stroke. Endothelial HIF-1 inhibition warrants further investigation as a therapeutic target for the treatment of stroke patients with diabetes.
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Registered trials
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