ArticlePharmaceutical research2017
Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury.
Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial.Clinical pharmacokinetics · 2018Trial
- Article
- Pharmacogenomics: Driving Personalized Medicine.Pharmacological reviews · 2023Review
- Article
- Valproic acid-induced changes of 4D nuclear morphology in astrocyte cells.Molecular biology of the cell · 2021Article
- Valproic acid treatment rescues injured tissues after traumatic brain injury.The journal of trauma and acute care surgery · 2020Article
- Histone Deacetylase Inhibitors: A Novel Strategy for Neuroprotection and Cardioprotection Following Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2020Review
- Druggable Transcriptional Networks in the Human Neurogenic Epigenome.Pharmacological reviews · 2019Review
- Deep learning in pharmacogenomics: from gene regulation to patient stratification.Pharmacogenomics · 2018Review
- Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury.Journal of neuroscience research · 2018Review
- The pharmacoepigenomics informatics pipeline defines a pathway of novel and known warfarin pharmacogenomics variants.Pharmacogenomics · 2018Article
- Transcriptomic changes following valproic acid treatment promote neurogenesis and minimize secondary brain injury.The journal of trauma and acute care surgery · 2018Article
- dbCoRC: a database of core transcriptional regulatory circuitries modeled by H3K27ac ChIP-seq signals.Nucleic acids research · 2018Article
- Trauma care: Finding a better way.PLoS medicine · 2017Article
- Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model.Resuscitation plusArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS).
methodsData were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases.
resultsThe transcriptional program in the CNS following TBI, HS, and VPA treatment includes activation of regulatory pathways that enhance neurogenesis and suppress gliogenesis. Genes which encode the transcription factors (TFs) that specify neuronal cell fate, including MEF2D, MYT1L, NEUROD1, PAX6 and TBR1, and their target genes, are induced by VPA. VPA represses genes responsible for oligodendrogenesis, maintenance of white matter, T-cell activation, angiogenesis, and endothelial cell proliferation, adhesion and chemotaxis. NEUROD1 has regulatory interactions with 38% of the genes regulated by VPA in a swine model of TBI and HS in adult brain. Hi-C spatial mapping of a VPA pharmacogenomic SNP in the GRIN2B gene shows it is part of a transcriptional hub that contacts 12 genes that mediate chromatin-mediated neurogenesis and neuroplasticity.
conclusionsFollowing TBI and HS, this study shows that VPA administration acts in the adult brain through differential activation of TFs responsible for neurogenesis, genes responsible for neuroplasticity, and repression of TFs that specify oligodendrocyte cell fate, endothelial cell chemotaxis and angiogenesis. Short title: Mechanism of action of valproic acid in traumatic brain injury.
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