title: Low dose of valproate improves motor function after traumatic brain injury.
abstract: BACKGROUND
  Traumatic brain injuries (TBIs) are a major health care problem worldwide. Approximately 1.5 million new TBI cases occur annually in the United States, with mortality rates ranging between 35% and 40% in severe patients. Despite the incidence of these injuries and their substantial socioeconomic implications, no specific pharmacological intervention is available for clinical use. Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate (VPA) exhibits neuroprotective effects in animal models. However, humans cannot tolerate high doses of VPA. This study aims to investigate whether 30 mg/kg of VPA administered to rats affects TBIs.
  
  
  METHODS
  We used a rat model to test the effects of 30 mg/kg of VPA on TBIs. Molecular identifications for histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) and phosphorylated extracellular signal regulated kinase (ERK) were performed.
  
  
  RESULTS
  The results indicated that treating adult rats with VPA after TBIs significantly decreased the contusion volume and recovery of contusion-related skilled forelimb reaching deficits. Applying VPA also increased histone acetylation, p-ERK, and p-CREB expression in the brain. Furthermore, applying VPA reduced inflammation, glial fibrillary acidic protein activation, and apoptosis. Conclusion. This study found that 30 mg/kg of VPA assists in treating TBIs in rat models.
authors.affiliation: Department of Anesthesiology, Taipei Medical University-Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tai
authors.affiliation: Department of Neurosurgery, China Medical University Hospital, China Medical University, Taipei Branch, Taipei, Taiwan.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Clinical Research Center, School of Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Fei-Peng
authors.initials: FP
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Clinical Research Center, Graduate Institute of Injury Prevention and Control, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan.
authors.forename: Tien-Jen
authors.initials: TJ
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Clinical Research Center, Graduate Institute of Injury Prevention and Control, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Shih
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Clinical Research Center, Graduate Institute of Injury Prevention and Control, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan.
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.affiliation: Department of Neurosurgery, Clinical Research Center, Graduate Institute of Injury Prevention and Control, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan.
authors.forename: Kuo-Sheng
authors.identifier: 0000-0002-4147-0960
authors.initials: KS
authors.lastname: Hung
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D014635:Valproic Acid; D048049:Extracellular Signal-Regulated MAP Kinases