ArticleThe journal of trauma and acute care surgery2020
Valproic acid treatment rescues injured tissues after traumatic brain injury.
Article in The journal of trauma and acute care surgery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Plasma and Imaging Biomarker Changes Following Rotational and Contusional Models of Traumatic Brain Injury in Adolescent Pigs.Journal of neurotrauma · 2026Article
- Valproic acid for treatment of traumatic brain injury: Study protocol for the VIBRANT prospective randomized trial.Transfusion · 2026Article
- Short-Term Cyclosporin A Treatment Reduced Serum Neurofilament-Light Levels in Diffuse but Not Focal Traumatic Brain Injury in a Piglet Model.Biomedicines · 2025Article
- Desorption Electrospray Ionization Cyclic Ion Mobility-Mass Spectrometry Imaging for Traumatic Brain Injury Spatial Metabolomics.Analytical chemistry · 2024Article
- Emerging Neuroprotective Strategies: Unraveling the Potential of HDAC Inhibitors in Traumatic Brain Injury Management.Current neuropharmacology · 2024Review
- Head Kinematics, Blood Biomarkers, and Histology in Large Animal Models of Traumatic Brain Injury and Hemorrhagic Shock.Journal of neurotrauma · 2023Article
- Neuroprotective agents effective against radiation damage of central nervous system.Neural regeneration research · 2022Review
- Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.The Journal of surgical research · 2021Article
- Validation of intraosseous delivery of valproic acid in a swine model of polytrauma.Trauma surgery & acute care open · 2021Article
- Brain proteomic changes by histone deacetylase inhibition after traumatic brain injury.Trauma surgery & acute care open · 2021Article
- Valproic Acid Inhibits Endoplasmic Reticulum Stress and Reduces Ferroptosis After Traumatic Brain Injury.Dose-response : a publication of International Hormesis SocietyArticle
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNo agents that are specifically neuroprotective are currently approved to emergently treat patients with traumatic brain injury (TBI). The histone deacetylase inhibitor, high-dose valproic acid (VPA) has been shown to have cytoprotective potential in models of combined TBI and hemorrhagic shock, but it has not been tested in an isolated TBI model. We hypothesized that VPA, administered after isolated TBI, will penetrate the injured brain, attenuate the lesion size, and activate prosurvival pathways.
methodsYorkshire swine were subjected to severe TBI by cortical impact. One hour later, animals were randomized to VPA treatment (150 mg/kg delivered intravenously for 1 hour; n = 4) or control (saline vehicle; n = 4) groups. Seven hours after injury, animals were sacrificed, and brain lesion size was measured. Mass spectrometry imaging was used to visualize and quantitate brain tissue distribution of VPA. Sequential serum samples were assayed for key biomarkers and subjected to proteomic and pathway analysis.
resultsBrain lesion size was 50% smaller (p = 0.01) in the VPA-treated animals (3,837 ± 948 mm) compared with the controls (1,900 ± 614 mm). Endothelial regions had eightfold higher VPA concentrations than perivascular regions by mass spectrometry imaging, and it readily penetrated the injured brain tissues. Serum glial fibrillary acid protein was significantly lower in the VPA-treated compared with the control animals (p < 0.05). More than 500 proteins were differentially expressed in the brain, and pathway analysis revealed that VPA affected critical modulators of TBI response including calcium signaling pathways, mitochondria metabolism, and biosynthetic machinery.
conclusionValproic acid penetrates injured brain tissues and exerts neuroprotective and prosurvival effects that resulted in a significant reduction in brain lesion size after isolated TBI. Levels of serum biomarkers reflect these changes, which could be useful for monitoring the response of TBI patients during clinical studies.
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