Valproic Acid Induces Pro-Survival Transcriptomic Changes in Swine Subjected to Traumatic Injury and Hemorrhagic Shock

BACKGROUND Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma. However, its protective mechanism of action is not completely understood. We sought to characterize the genetic changes induced by VPA treatment following traumatic injuries. METHODS Six female Yorkshire swine were subjected to traumatic brain injury (TBI, controlled cortical impact), polytrauma (liver and splenic laceration, rib fracture, rectus crush), and hemorrhagic shock (HS, 40% total blood volume). Following two hours of HS, animals were randomized to resuscitation with normal saline (NS) or NS + 150 mg/kg of intravenous VPA (n = 3/cohort, 18 samples total). Blood samples were collected for isolation of peripheral blood mononuclear cells (PBMCs) at three distinct time points: baseline, 6 hours following injuries, and on post-injury day 1 (PID1). RNA was extracted from PBMCs and sequenced. Differential expression analysis (false discovery rate

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