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J Neurosci Res. 2018 Apr;96(4):711-719. doi: 10.1002/jnr.24125. Epub 2017 Jul 25.

Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury.

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Department of Surgery, University of Michigan Hospital, Ann Arbor, Michigan.
Department of Neurological Surgery, Case Western Reserve University, Cleveland, Ohio.
Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.
Department of Surgical Gastroenterology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.


Traumatic brain injury (TBI) is a leading cause of death in young adults, and effective treatment strategies have the potential to save many lives. 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-generation 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-generation 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.


histone deacetylase inhibitor; resuscitation; traumatic brain injury; valproic acid

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