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TBI results in coagulopathy, endothelial dysfunction, inflammation, cell death, and impaired epigenetic homeostasis, ultimately leading to morbidity and\/or mortality. Commonly used resuscitation fluids such as crystalloids or colloids have several disadvantages and might even be harmful when administered in large quantities. There is a need for next\u2010generation treatment strategies (especially in the prehospital setting) that minimize cellular damage, improve survival, and enhance neurological recovery. Pharmacologic treatment with histone deacetylase inhibitors, such as valproic acid, has shown promising results in animal studies of TBI and may therefore be an excellent example of next\u2010generation therapy. This review briefly describes traditional resuscitation strategies for TBI combined with hemorrhagic shock and describes preclinical studies on valproic acid as a new pharmacologic agent in the treatment of TBI. It finally discusses limitations and future directions on the use of histone deacetylase inhibitors for the treatment of TBI.<\/jats:p>","DOI":"10.1002\/jnr.24125","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T15:52:36Z","timestamp":1500997956000},"page":"711-719","source":"Crossref","is-referenced-by-count":22,"title":["Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury"],"prefix":"10.1002","volume":"96","author":[{"given":"Simone E.","family":"Dekker","sequence":"first","affiliation":[{"name":"Department of Surgery University of Michigan Hospital Ann Arbor Michigan"},{"name":"Department of Neurological Surgery Case Western Reserve University Cleveland Ohio"},{"name":"Department of Anesthesiology, Institute for Cardiovascular Research VU University Medical Center Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahagn C.","family":"Nikolian","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Hospital Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sillesen","sequence":"additional","affiliation":[{"name":"Department of Surgical Gastroenterology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"},{"name":"Institute for Inflammation Research Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Bambakidis","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Hospital Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Schober","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Institute for Cardiovascular Research VU University Medical Center Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1024-5226","authenticated-orcid":false,"given":"Hasan B.","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Hospital Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,25]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"90","article-title":"Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science","volume":"16","author":"Abdanipour A.","year":"2012","journal-title":"Iranian Biomedical Journal"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9572(02)00095-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2009.04.007"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/j.cpsurg.2011.04.002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e31820d0dcc"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3171\/2012.11.JNS12622"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10903120701732052"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.4163"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0000000000000626"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.033"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199410273311701"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3181271ba3"},{"key":"e_1_2_8_14_1","first-page":"59","article-title":"Screening of potential small volume resuscitation products using a severe hemorrhage sedated swine model","volume":"2","author":"Burns J. 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