ArticleExperimental neurology2016
Fetal stress-mediated hypomethylation increases the brain susceptibility to hypoxic-ischemic injury in neonatal rats.
Article in Experimental neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
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- Article
- STZ-induced gestational diabetes exposure alters PTEN/AKT/mTOR-mediated autophagy signaling pathway leading to increase the risk of neonatal hypoxic-ischemic encephalopathy.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes.Cell & bioscience · 2023Article
- Brain-targeted hypoxia-inducible factor stabilization reduces neonatal hypoxic-ischemic brain injury.Neurobiology of disease · 2021Article
- Gestational Hypoxia and Blood-Brain Barrier Permeability: Early Origins of Cerebrovascular Dysfunction Induced by Epigenetic Mechanisms.Frontiers in physiology · 2021Review
- Epigenetics modifiers: potential hub for understanding and treating neurodevelopmental disorders from hypoxic injury.Journal of neurodevelopmental disorders · 2020Review
- Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage.Frontiers in neurology · 2020Review
- Antenatal Hypoxia Accelerates the Onset of Alzheimer's Disease Pathology in 5xFAD Mouse Model.Frontiers in aging neuroscience · 2020Article
- Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?Current genomics · 2018Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Inhibition of Connexin 43 Hemichannels Alleviates Cerebral Ischemia/Reperfusion Injury via the TLR4 Signaling Pathway.Frontiers in cellular neuroscience · 2018Article
- Ischemic-Reperfusion Injury Increases Matrix Metalloproteinases and Tissue Metalloproteinase Inhibitors in Fetal Sheep Brain.Developmental neuroscience · 2018Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeFetal hypoxia increases brain susceptibility to hypoxic-ischemic (HI) injury in neonatal rats. Yet mechanisms remain elusive. The present study tested the hypothesis that DNA hypomethylation plays a role in fetal stress-induced increase in neonatal HI brain injury.
methodsPregnant rats were exposed to hypoxia (10.5% O2) from days 15 to 21 of gestation and DNA methylation was determined in the developing brain. In addition, 5-aza-2'-deoxycytidine (5-Aza) was administered in day 7 pups brains and the HI treatment was conducted in day 10 pups. Brain injury was determined by in vivo MRI 48 h after the HI treatment and neurobehavioral function was evaluated 6 weeks after the HI treatment.
resultsFetal hypoxia resulted in DNA hypomethylation in the developing brain, which persisted into 30-day old animals after birth. The treatment of neonatal brains with 5-Aza induced similar hypomethylation patterns. Of importance, the 5-Aza treatment significantly increased HI-induced brain injury and worsened neurobehavioral function recovery six weeks after the HI-treatment. In addition, 5-Aza significantly increased HIF-1α mRNA and protein abundance as well as matrix metalloproteinase (MMP)-2 and MMP-9, but decreased MMP-13 protein abundance in neonatal brains. Consistent with the 5-Aza treatment, hypoxia resulted in significantly increased expression of HIF-1α in both fetal and neonatal brains. Inhibition of HIF-1α blocked 5-Aza-mediated changes in MMPs and abrogated 5-Aza-induced increase in HI-mediated brain injury.
conclusionThe results suggest that fetal stress-mediated DNA hypomethylation in the developing brain causes programming of hypoxic-ischemic sensitive phenotype in the brain and increases the susceptibility of neonatal brain to hypoxic-ischemic injury in a HIF-1α-dependent manner.
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