Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in a large animal model of traumatic brain injury and hemorrhagic shock

• Published in: The Journal of surgical research 2014-07, Vol.190 (1), p.312-318
• Main Authors: Dekker, Simone E., BSc, Sillesen, Martin, MD, Bambakidis, Ted, MSc, Andjelkovic, Anuska V., MD, PhD, Jin, Guang, MD, PhD, Liu, Baoling, MD, Boer, Christa, PhD, Johansson, Pär I., MD, Dmsc, MPA, Linzel, Durk, MD, Halaweish, Ihab, MD, Alam, Hasan B., MD
• Format: Article
• Language: English
• Subjects: Animals; Brain Injuries - blood; Brain Injuries - drug therapy; CD40 Ligand - blood; Disease Models, Animal; Female; Fresh frozen plasma; Hemorrhagic shock; Histone deacetylase inhibitor; Histone Deacetylase Inhibitors - administration & dosage; Neuroprotection; P-Selectin - blood; Platelet activation; Platelet Activation - drug effects; Resuscitation; Shock, Hemorrhagic - blood; Shock, Hemorrhagic - drug therapy; Surgery; Swine; Traumatic brain injury; Valproic Acid - administration & dosage
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2014.02.049

Abstract Background We have previously shown that resuscitation with fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) decreases the size of the brain lesion, and that addition of a histone deacetylase inhibitor, valproic acid (VPA), provides synergistic benefits. In this study, we hypothesized that VPA administration would be associated with a conservation of platelet function as measured by increased platelet activation after resuscitation. Materials and methods Ten swine (42-50 kg) were subjected to TBI and HS (40% blood loss). Animals were left in shock for 2 h before resuscitation with either FFP or FFP + VPA (300 mg/kg). Serum levels of platelet activation markers transforming growth factor beta, CD40 L, P-selectin, and platelet endothelial cell adhesion molecule (PECAM) 1 were measured at baseline, postresuscitation, and after a 6-h observation period. Platelet activation markers were also measured in the brain whole cell lysates and immunohistochemistry. Results Circulating P-selectin levels were significantly higher in the FFP + VPA group compared with the FFP alone group (70.85 ± 4.70 versus 48.44 ± 7.28 ng/mL; P