@article{6ceba5fe50834931a290a330f02d2a97,
title = "Creating a {"}Prosurvival phenotype{"} through histone deacetylase inhibition: Past, present, and future",
abstract = "Traumatic injuries and their sequelae represent a major source of mortality in the United States and globally. Initial treatment for shock, traumatic brain injury, and polytrauma is limited to resuscitation fluids to replace lost volume. To date there are no treatments with inherent prosurvival properties. Our laboratory has investigated the use of histone deacetylase inhibitors (HDACIs) as pharmacological agents to improve survival. This class of drugs acts through posttranslational protein modifications and is a direct regulator of chromatin structure and function, as well as the function of numerous cytoplasmic proteins. In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a significant survival advantage, even in the absence of fluid resuscitation. Positive results have also been shown in two-hit models of hemorrhage and sepsis and in hemorrhagic shock combined with traumatic brain injury. Accumulating data generated by our group and others continue to support the use of HDACIs for the creation of a prosurvival phenotype. With further research and clinical trials, HDACIs have the potential to be an integral tool in the treatment of trauma, especially in the prehospital phase.",
keywords = "Epigenetic, Genes, Hemorrhage, Histone deacetylase inhibitor, Inflammation, Proteins, Sepsis, Shock, Survival, Traumatic brain injury",
author = "Ihab Halaweish and Vahagn Nikolian and Patrick Georgoff and Yongqing Li and Alam, {Hasan B.}",
note = "Funding Information: be further exaggerated by inappropriate resuscitation (11). Therefore, contemporary trauma care is moving rapidly away from aggressive crystalloid infusion toward Bdamage control resuscitation[ that promotes minimal use of crystalloids, rapid hemorrhage control, and early administration of blood components (red blood cells, plasma, and platelets) (12Y15). However, use of blood products is not practical in the pre-hospital setting where most of the deaths occur, and especially in the battlefield. This has fueled an initiative to develop novel life-preserving strategies that could serve as a bridge to definitive care. Our team, through funding from the Department of Defense and the National Institutes of Health, has pursued the development of pharmacological interventions that could alter the cellular response to injury and create a Bprosurvival phenotype.[ Funding Information: Dr. Alam acknowledges research support provided by numerous grants from the Office of Naval Research (including N000140910378 and N000141310071), the US Army Medical Research and Materiel Command (W81XWH-09-1-0520), the Defense Advanced Research Projects Agency(W911NF-06-1-0220), and theNational Institutes of Health (R01GM084127). Funding Information: Dr. Alam acknowledges research support provided by numerous grants from the Office of Naval Research (including N000140910378 and N000141310071), the US Army Medical Research and Materiel Command (W81XWH-09-1-0520), the Defense Advanced Research Projects Agency (W911NF-06-1-0220), and the National Institutes of Health (R01GM084127). Dr. Alam also received a research grant from the Massey Foundation to study traumatic brain injury. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense at large. The authors have no financial conflict of interest. DOI: 10.1097/SHK.0000000000000319 Copyright {\textcopyright} 2015 by the Shock Society Publisher Copyright: Copyright {\textcopyright} 2015 by the Shock Society.",
year = "2015",
month = aug,
doi = "10.1097/SHK.0000000000000319",
language = "English (US)",
volume = "44",
pages = "6--16",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
}