ArticleNeurobiology of disease2021
Brain-targeted hypoxia-inducible factor stabilization reduces neonatal hypoxic-ischemic brain injury.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Intranasal therapies for neonatal hypoxic-ischemic encephalopathy.Neural regeneration research · 2026Article
- Morphological Changes in the Rat Brain in the Early Post-Resuscitation Period: The Relationship Between Hypoxia-Sensitive Immunohistochemical Markers, Hemodynamic and Acid-Base Status.International journal of molecular sciences · 2026Article
- Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.Journal of physiology and biochemistry · 2026Review
- Neurological Effects ofNutrients · 2026Article
- Mechanical compression induces neuronal apoptosis, reduces synaptic activity, and promotes glial neuroinflammation in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Inhibition of the HIF-1α Signaling Pathway Promotes Oligodendrocyte Maturation in the In Vitro Model of Perinatal Asphyxia.Molecular neurobiology · 2025Article
- Dual-modal metabolic analysis reveals hypothermia-reversible uncoupling of oxidative phosphorylation in neonatal brain hypoxia-ischemia.bioRxiv : the preprint server for biology · 2025Article
- The salivary metabolomics analyses reveal the variable metabolites in distinct staging of periodontitis.BMC oral health · 2025Article
- Lactate accumulation from HIF-1α-mediated PMN-MDSC glycolysis restricts brain injury after acute hypoxia in neonates.Journal of neuroinflammation · 2025Article
- Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury.Current topics in medicinal chemistry · 2025Review
- Melatonin Inhibits Hypoxia-Induced Alzheimer's Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells.International journal of molecular sciences · 2024Article
- Further Evidence of Neuroprotective Effects of Recombinant Human Erythropoietin and Growth Hormone in Hypoxic Brain Injury in Neonatal Mice.International journal of molecular sciences · 2022Article
- Therapeutic angiogenesis-based strategy for peripheral artery disease.Theranostics · 2022Review
- Therapeutic potential and molecular mechanisms of salidroside in ischemic diseases.Frontiers in pharmacology · 2022Review
- Thiamine as a Possible Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Encephalopathy.Antioxidants (Basel, Switzerland) · 2021Review
- Creatine transporter deficiency impairs stress adaptation and brain energetics homeostasis.JCI insight · 2021Article
- Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke.Frontiers in immunology · 2021Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor-1α (HIF1α) is a major regulator of cellular adaptation to hypoxia and oxidative stress, and recent advances of prolyl-4-hydroxylase (P4H) inhibitors have produced powerful tools to stabilize HIF1α for clinical applications. However, whether HIF1α provokes or resists neonatal hypoxic-ischemic (HI) brain injury has not been established in previous studies. We hypothesize that systemic and brain-targeted HIF1α stabilization may have divergent effects. To test this notion, herein we compared the effects of GSK360A, a potent P4H inhibitor, in in-vitro oxygen-glucose deprivation (OGD) and in in-vivo neonatal HI via intracerebroventricular (ICV), intraperitoneal (IP), and intranasal (IN) drug-application routes. We found that GSK360A increased the erythropoietin (EPO), heme oxygenase-1 (HO1) and glucose transporter 1 (Glut1) transcripts, all HIF1α target-genes, and promoted the survival of neurons and oligodendrocytes after OGD. Neonatal HI insult stabilized HIF1α in the ipsilateral hemisphere for up to 24 h, and either ICV or IN delivery of GSK360A after HI increased the HIF1α target-gene transcripts and decreased brain damage. In contrast, IP-injection of GSK360A failed to reduce HI brain damage, but elevated the risk of mortality at high doses, which may relate to an increase of the kidney and plasma EPO, leukocytosis, and abundant vascular endothelial growth factor (VEGF) mRNAs in the brain. These results suggest that brain-targeted HIF1α-stabilization is a potential treatment of neonatal HI brain injury, while systemic P4H-inhibition may provoke unwanted adverse effects.
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