ArticleMolecular neurobiology2023
Histone Deacetylase 3 Inhibition Decreases Cerebral Edema and Protects the Blood-Brain Barrier After Stroke.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- 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
- A2 astrocyte polarization mediates ketogenic diet protection of blood-central nervous system barriers in experimental autoimmune encephalomyelitis.Neural regeneration research · 2026Article
- Metabolic-Epigenetic-Immune axis in Ischemic Stroke: Lactate-derived Lactylation as a Key Regulator.Metabolic brain disease · 2026Review
- Histone decrotonylation plays a distinct role in HIV latency.Science advances · 2026Article
- β-Hydroxybutyrate improves glymphatic system function and alleviates cerebral edema in mice after ischemic stroke.Acta pharmacologica Sinica · 2026Article
- Targeting epigenetic remodeling of the blood-brain barrier: current knowledge for drug therapy.Epigenomics · 2026Review
- Histone and non-histone (de)acetylation impact on the blood-brain barrier.Fluids and barriers of the CNS · 2026Review
- HDAC3 Mediates Hippocampal Microglial Pyroptosis Via the STING/NLRP3 Pathway and Contributes To Cognitive Impairment in Sepsis-Associated Encephalopathy.Inflammation · 2026Article
- Targeting Epigenetics in Ischemic Stroke: From Mechanisms to Therapeutics.Current neuropharmacology · 2026Review
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- HDAC3 as an Emerging Therapeutic Target for Alzheimer's Disease and other Neurological Disorders.Molecular neurobiology · 2025Review
- Unraveling the role of HDAC3 as an immunotherapy prognostic biomarker and therapeutic target in advanced non-small cell lung cancer.Respiratory research · 2025Article
- Protective effects of sesamol against cigarette smoke toxicity on the blood-brain barrier.BMC complementary medicine and therapies · 2025Article
- Article
- Microglial Mechanisms and Therapeutic Potential in Brain Injury Post-Intracerebral Hemorrhage.Journal of inflammation research · 2025Review
- HDAC3 in action: Expanding roles in inflammation and inflammatory diseases.Cell proliferation · 2025Review
- Inhibition of HDAC3 induces neuroprotection by activating the Npas4 signaling pathway following surgical brain injury in rats.Iranian journal of basic medical sciences · 2025Article
- Inhibition of the AP-1/TFPI2 axis contributes to alleviating cerebral ischemia/reperfusion injury by improving blood-brain barrier integrity.Human cell · 2024Article
- Role of transcription factors, noncoding RNAs, epitranscriptomics, and epigenetics in post-ischemic neuroinflammation.Journal of neurochemistry · 2024Review
- Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation.Cellular & molecular biology letters · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
We have previously shown that selective inhibition of histone deacetylase 3 (HDAC3) decreases infarct volume and improves long-term functional outcomes after stroke. In this study, we examined the effects of HDAC3 inhibition on cerebral edema and blood-brain barrier (BBB) leakage and explored its underlying mechanisms. Adult male Wistar rats were subjected to 2-h middle cerebral artery occlusion (MCAO) and randomly treated i.p. with either vehicle or a selective HDAC3 inhibitor (RGFP966) at 2 and 24 h after stroke. Modified neurological severity scores (mNSS) were calculated at 2 h, 1 day, and 3 days. H&E, Evans blue dye (EBD) assay, and fluorescein isothiocyanate (FITC)-dextran were employed to assess cerebral edema and BBB leakage. Western blot for matrix metalloproteinase-9 (MMP9), MMP-9 zymography, and immunostaining for HDAC3, GFAP, Iba-1, albumin, aquaporin-4, claudin-5, ZO-1, and NF-kB were performed. Early RGFP966 administration decreased cerebral edema (p = 0.002) and BBB leakage, as measured by EBD assay, FITC-dextran, and albumin extravasation (p < 0.01). RGFP966 significantly increased tight junction proteins (claudin-5 and ZO-1) in the peri-infarct area. RGFP966 also significantly decreased HDAC3 in GFAP + astrocytes, which correlated with better mNSS (r = 0.67, p = 0.03) and decreased cerebral edema (r = 0.64, p = 0.04). RGFP966 decreased aquaporin-4 in GFAP + astrocytes (p = 0.002), as well as, the inflammatory markers Iba-1, NF-kB, and MMP9 in the ischemic brain (p < 0.05). Early HDAC3 inhibition decreases cerebral edema and BBB leakage. BBB protection by RGFP966 is mediated in part by the upregulation of tight junction proteins, downregulation of aquaporin-4 and HDAC3 in astrocytes, and decreased neuroinflammation.
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