title: Extracellular signal-regulated kinase 1/2 is involved in a tamoxifen neuroprotective effect in a lateral fluid percussion injury rat model.
abstract: BACKGROUND
  The aim of the present study was to determine whether tamoxifen (TMX) causes attenuation of traumatic brain injury (TBI) induced by fluid percussion injury.
  
  
  METHODS
  Immediately after the onset of fluid percussion TBI, anesthetized male Sprague-Dawley rats were divided into three major groups and intraperitoneally administered the vehicle solution (1 mL/kg), TMX (1 mg/kg), or TMX (1 mg/kg) plus the extracellular signal-regulated kinase 1/2 antagonist SL327 (30 mg/kg). Another group of rats were used as sham-operated controls. The functional outcomes, such as motor outcomes, were evaluated using an incline plane. The cellular infarction volume was evaluated by triphenyltetrazolium chloride staining. Neuronal loss, apoptosis, and p-ERK1/2 and Bcl2 expression in neuronal cortex cells were evaluated by immunofluorescence methods. All the parameters were assessed on day 4 after injury.
  
  
  RESULTS
  Compared with the sham-operated controls, the TBI-induced motor deficits and cerebral infarction after TBI were significantly attenuated by TMX therapy. The TBI-induced neuronal loss and apoptosis were also significantly reduced by TMX therapy. The numbers of Bcl2- and phospho-ERK1/2-positive neuronal cells in the ischemic cortex after TBI were significantly increased by TMX therapy. These TMX effects were significantly blocked by SL327 administration.
  
  
  CONCLUSIONS
  Our results suggest that intravenous injection of TMX may ameliorate TBI in rats by increasing neuronal p-ERK1/2 expression, which might lead to an increase in neuronal Bcl2 expression and a decrease in neuronal apoptosis and cell infarction volume, and it might represent one mechanism by which functional recovery occurred. TMX may be a promising TBI treatment strategy.
authors.affiliation: Department of intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Yin-Tzu
authors.initials: YT
authors.lastname: Tsai
authors.affiliation: Department of Neurosurgery, Tainan, Taiwan; Institute of Photonic Systems, National Chiao-Tung University, Tainan, Taiwan; Department of Child Care, Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Che-Chuan
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Pak-On
authors.initials: PO
authors.lastname: Leung
authors.affiliation: Department of Medical Research Chi-Mei Medical Center, Tainan, Taiwan; Department of Biotechnology, Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Kao-Chang
authors.initials: KC
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Tainan, Taiwan.
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chio
authors.affiliation: Department of Medical Research Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Chiao-Ya
authors.initials: CY
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Tainan, Taiwan; Department of Medical Research Chi-Mei Medical Center, Tainan, Taiwan; Department of Biotechnology, Taiwan University of Science and Technology, Tainan, Taiwan. Electronic address: kuojinnrung@gmail.com.
authors.forename: Jinn-Rung
authors.initials: JR
authors.lastname: Kuo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1
keywords: Cell apoptosis; Extracellular signal–regulated kinases (ERK1/2); Fluid percussion injury; Infarction volume; Maximal angle; Tamoxifen