Valproic acid treatment rescues injured tissues after traumatic brain injury
| العنوان: | Valproic acid treatment rescues injured tissues after traumatic brain injury |
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| المؤلفون: | Alizeh Shamshad, Henriette A. Remmer, Ariella M. Iancu, Luke Pumiglia, Hasan B. Alam, Rachel L. O'Connell, Glenn K. Wakam, Ben E. Biesterveld, Ali Z. Siddiqui, Manjunath P. Pai, Michael T. Kemp, Aaron M. Williams |
| المصدر: | J Trauma Acute Care Surg |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Proteomics, Swine, medicine.drug_class, Traumatic brain injury, medicine.medical_treatment, Shock, Hemorrhagic, Pharmacology, Critical Care and Intensive Care Medicine, Neuroprotection, Article, Lesion, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Brain Injuries, Traumatic, Glial Fibrillary Acidic Protein, Animals, Medicine, Distribution (pharmacology), Saline, Valproic Acid, business.industry, Histone deacetylase inhibitor, Brain, 030208 emergency & critical care medicine, Metabolism, medicine.disease, Histone Deacetylase Inhibitors, Disease Models, Animal, Female, lipids (amino acids, peptides, and proteins), Surgery, medicine.symptom, business, Biomarkers, medicine.drug |
| الوصف: | BACKGROUND: No 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 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 pro-survival pathways. METHODS: Yorkshire swine were subjected to severe TBI by cortical impact. One hour later, animals were randomized to VPA treatment (150 mg/kg delivered intravenously over 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 (MS) 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. RESULTS: Brain lesion size was 50% smaller (p=0.01) in the VPA treated animals (3837±948 mm(3)) compared to the controls (1900±614 mm(3)). Endothelial regions had 8-fold higher VPA concentrations than perivascular regions by MS-imaging, and it readily penetrated the injured brain tissues. Serum glial fibrillary acid protein was significantly lower in the VPA-treated compared to the control animals (p |
| تدمد: | 2163-0763 2163-0755 |
| DOI: | 10.1097/ta.0000000000002918 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7cb20a8a17c7748f5c2c509e9691bd27 https://doi.org/10.1097/ta.0000000000002918 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7cb20a8a17c7748f5c2c509e9691bd27 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21630763 21630755 |
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| DOI: | 10.1097/ta.0000000000002918 |