Evidence map›Paper›PMID 27722928›Full record

ArticleMolecular neurobiology2017

HDAC Inhibitor Sodium Butyrate-Mediated Epigenetic Regulation Enhances Neuroprotective Function of Microglia During Ischemic Stroke.

Radhika Patnala, Thiruma V Arumugam, Neelima Gupta, S Thameem Dheen

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 5 pooled it
5.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

174 citing papers in PubMed, 5 syntheses or guidelines pooled it, 259 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Article
  8. Review
  9. The gut-heart axis in cardio-oncology.Cardiovascular research · 2026
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  13. Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026
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  14. Review
  15. Butyrate Is Associated with the Antidepressant Effects ofInternational journal of molecular sciences · 2026
    Article
  16. Article
  17. Gut-Brain Signaling in Parkinson's Disease: A Narrative Review.International journal of molecular sciences · 2026
    Review
  18. Review
  19. Review
  20. Article

114 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Radhika PatnalaDepartment of Anatomy, The Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore.
Thiruma V ArumugamDepartment of Physiology, The Yong Loo Lin School of Medicine, National University of Singapore, MD9, 2 Medical Drive, Singapore, 117597, Singapore.
Neelima GuptaDepartment of Anatomy, The Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore.
S Thameem DheenDepartment of Anatomy, The Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore. antstd@nus.edu.sg.
National University of Singapore · SG

Funding

National University Health System seed fund for basic science research T1-BSRG 2014-02
6 · The paper itself

Abstract

Cerebral ischemia leads to neuroinflammation and activation of microglia which further contribute to stroke pathology. Understanding regulation of microglial activation will aid in the development of therapeutic strategies that mitigate microglia-mediated neurotoxicity in neuropathologies, including ischemia. In this study, we investigated the epigenetic regulation of microglial activation by studying histone modification histone 3-lysine 9-acetylation (H3K9ac) and its regulation by histone deacetylase (HDAC) inhibitors. In vitro analysis of activated microglia showed that HDAC inhibitor, sodium butyrate (SB), alters H3K9ac enrichment and transcription at the promoters of pro-inflammatory (Tnf-α, Nos2, Stat1, Il6) and anti-inflammatory (Il10) genes while inducing the expression of genes downstream of the IL10/STAT3 anti-inflammatory pathway. In an experimental mouse (C57BL/6NTac) model of middle cerebral artery occlusion (MCAO), we observed that SB mediates neuroprotection by epigenetically regulating the microglial inflammatory response, via downregulating the expression of pro-inflammatory mediators, TNF-α and NOS2, and upregulating the expression of anti-inflammatory mediator IL10, in activated microglia. Interestingly, H3K9ac levels were found to be upregulated in activated microglia distributed in the cortex, striatum, and hippocampus of MCAO mice. A similar upregulation of H3K9ac was detected in lipopolysaccharide (LPS)-activated microglia in the Wistar rat brain, indicating that H3K9ac upregulation is consistently associated with microglial activation in vivo. Altogether, these results show evidence of HDAC inhibition being a promising molecular switch to epigenetically modify microglial behavior from pro-inflammatory to anti-inflammatory which could mitigate microglia-mediated neuroinflammation.

Indexed as

AnimalsBrainBrain IschemiaButyric AcidCells, CulturedEpigenesis, GeneticGene Expression RegulationHistone Deacetylase InhibitorsMaleMiceMicrogliaNeuroprotective AgentsRatsRats, WistarStrokeButyric AcidHistone Deacetylase InhibitorsNeuroprotective AgentsEpigeneticsH3K9acHDAC inhibitorsIschemiaMicrogliaNeuroinflammation

Identifiers

PMID27722928
OpenAlexW2529049144

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.