ArticleFree radical biology & medicine2012
Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
123 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Role of histone deacetylases and sirtuins in the ischaemic stroke: a systematic review and meta-analysis of animal studies.Stroke and vascular neurology · 2026Pooled it
- Pooled it
- Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.Translational research : the journal of laboratory and clinical medicine · 2019Pooled it
- Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.Scientific reports · 2016Pooled it
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation.Cell death & disease · 2026Article
- Histone and non-histone (de)acetylation impact on the blood-brain barrier.Fluids and barriers of the CNS · 2026Review
- Molecular Mechanisms Underlying Atherosclerosis and Current Advances in Targeted Therapeutics.International journal of molecular sciences · 2026Review
- Protein acetylation in atherosclerosis: beyond inflammation to core cellular processes and therapeutic potential.Frontiers in immunology · 2026Review
- Sodium Phenylbutyrate Ameliorates Ovariectomy-Induced Bone Loss in Rats.Medicina (Kaunas, Lithuania) · 2025Article
- Extracellular vesicles from adipose-derived mesenchymal stem cells prevent high glucose-induced retinal ganglion cell pyroptosis through a microRNA-26a-5p-dependent mechanism.Journal of diabetes investigation · 2025Article
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Synergistic Antioxidant Effects of C3G-EnrichedInternational journal of molecular sciences · 2025Article
- Article
- Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.Molecular neurobiology · 2025Review
- Phytochemical, In Silico, In Vitro, and In Vivo Research on Piptadeniastrum africanum (Fabaceae) Unveiling Anti-Stereotypic, Anxiolytic, and Analgesic Effects in a Sodium Valproate-Induced Autistic Disorders Model.Brain and behavior · 2025Article
- HDAC3 in action: Expanding roles in inflammation and inflammatory diseases.Cell proliferation · 2025Review
- Commentary: Synergistic treatment of sodium propionate and Sishen Pill for diarrhea mice with kidney-yang deficiency syndrome.Frontiers in cellular and infection microbiology · 2025Article
- Nanoparticle-based itaconate treatment recapitulates low-cholesterol/low-fat diet-induced atherosclerotic plaque resolution.Cell reports · 2024Article
- Molecular Targeting of Ischemic Stroke: The Promise of Naïve and Engineered Extracellular Vesicles.Pharmaceutics · 2024Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Interest in histone deacetylase (HDAC)-based therapeutics as a potential treatment for stroke has grown dramatically. The neuroprotection of HDAC inhibition may involve multiple mechanisms, including modulation of transcription factor acetylation independent of histones. The transcription factor Nrf2 has been shown to be protective in stroke as a key regulator of antioxidant-responsive genes. Here, we hypothesized that HDAC inhibition might provide neuroprotection against mouse cerebral ischemia by activating the Nrf2 pathway. We determined that the classic HDAC inhibitor trichostatin A increased neuronal cell viability after oxygen-glucose deprivation (from an OD value of 0.10±0.01 to 0.25±0.08) and reduced infarct volume in wild-type mice with stroke (from 49.1±3.8 to 21.3±4.6%). In vitro studies showed that HDAC inhibition reduced Nrf2 suppressor Keap1 expression, induced Keap1/Nrf2 dissociation, Nrf2 nuclear translocation, and Nrf2 binding to antioxidant response elements in heme oxygenase 1 (HO1), and caused HO1 transcription. Furthermore, we demonstrated that HDAC inhibition upregulated proteins downstream of Nrf2, including HO1, NAD(P)H:quinone oxidoreductase 1, and glutamate-cysteine ligase catalytic subunit in neuron cultures and brain tissue. Finally, unlike wild-type mice, Nrf2-deficient mice were not protected by pharmacologic inhibition of HDAC after cerebral ischemia. Our studies suggest that activation of Nrf2 might be an important mechanism by which HDAC inhibition provides neuroprotection.
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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.