ArticleMolecular neurobiology2019
Inhibition of the Epigenetic Regulator REST Ameliorates Ischemic Brain Injury.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- siRNA for REST ameliorates symptoms in ALS mice and serum REST predicts disease prognosis and survival in ALS patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Expression Profiles of Genes Related to Serotonergic Synaptic Function in Hypothalamus of Hypertensive and Normotensive Rats in Basal and Stressful Conditions.International journal of molecular sciences · 2025Article
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- Synergistic effects of repeated transcranial magnetic stimulation and mesenchymal stem cells transplantation on alleviating neuroinflammation and PANoptosis in cerebral ischemia.Journal of neuroinflammation · 2024Article
- Ischemic Stroke and the Biological Hallmarks of Aging.Aging and disease · 2024Review
- Stroke Causes DNA Methylation atJournal of the American Heart Association · 2024Article
- Post-stroke brain can be protected by modulating the lncRNA FosDT.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- REST in the Road Map of Brain Development.Cellular and molecular neurobiology · 2023Review
- REST contributes to AKI-to-CKD transition through inducing ferroptosis in renal tubular epithelial cells.JCI insight · 2023Article
- Epigenetic mechanisms and potential therapeutic targets in stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia.Metabolic brain disease · 2021Review
- TET3 regulates DNA hydroxymethylation of neuroprotective genes following focal ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Epigenetic mechanisms of neurodegenerative diseases and acute brain injury.Neurochemistry international · 2020Review
- Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage.Frontiers in neurology · 2020Review
- Melatonin Plays a Protective Role by Regulating miR-26a-5p-NRSF and JAK2-STAT3 Pathway to Improve Autophagy, Inflammation and Oxidative Stress of Cerebral Ischemia-Reperfusion Injury.Drug design, development and therapy · 2020Article
- Statistical differences resulting from selection of stable reference genes after hypoxia and hypothermia in the neonatal rat brain.PloS one · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cerebral ischemia is known to activate the repressor element-1 (RE1)-silencing transcription factor (REST) which silences neural genes via epigenetic remodeling and promotes neurodegeneration. We presently determined if REST inhibition derepresses target genes involved in synaptic plasticity and promotes functional outcome after experimental stroke. Following transient focal ischemia induced by middle cerebral artery occlusion (MCAO) in adult rats, REST expression was upregulated significantly from 12 h to 1 day of reperfusion compared to sham control. At 1 day of reperfusion, REST protein levels were increased and observed in the nuclei of neurons in the peri-infarct cortex. REST knockdown by intracerebral REST siRNA injection significantly reduced the post-ischemic expression of REST and increased the expression of several REST target genes, compared to control siRNA group. REST inhibition also decreased post-ischemic markers of apoptosis, reduced cortical infarct volume, and improved post-ischemic functional recovery on days 5 and 7 of reperfusion compared to the control siRNA group. REST knockdown resulted in a global increase in synaptic plasticity gene expression at 1 day of reperfusion compared to the control siRNA group and significantly increased several synaptic plasticity genes containing RE-1 sequences in their regulatory regions. These results demonstrate that direct inhibition of the epigenetic remodeler REST prevents secondary brain damage in the cortex and improves functional outcome potentially via de-repression of plasticity-related genes after stroke.
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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.