title: Tamoxifen as an effective neuroprotectant against early brain injury and learning deficits induced by subarachnoid hemorrhage: possible involvement of inflammatory signaling.
abstract: BACKGROUND
  Tamoxifen, a selective estrogen receptor modulator, has successfully been used to treat several animal models of brain injury, but the underlying mechanisms remain unclear. This study was undertaken to evaluate the effect of tamoxifen on the toll-like receptor 4 (TLR4)- and nuclear factor-κB (NF-κB)-related inflammatory signaling pathway and secondary brain injury in rats after subarachnoid hemorrhage (SAH).
  
  
  METHODS
  Adult male Sprague-Dawley rats were divided into four groups: (1) control group (n = 28); (2) SAH group (n = 28); (3) SAH + vehicle group (n = 28); and (4) SAH + tamoxifen group (n = 28). All SAH animals were subjected to injection of autologous blood into the prechiasmatic cistern once on day 0. In SAH + tamoxifen group, tamoxifen was administered intraperitoneally at a dose of 5 mg/kg at 2 h, 12 h, and 36 h after SAH. In the first set of experiments, brain samples were extracted and evaluated at 48 h after SAH. In the second set of experiments, the Morris water maze was used to investigate cognitive and memory changes.
  
  
  RESULTS
  We found that treatment with tamoxifen markedly inhibited the protein expressions of TLR4, NF-κB and the downstream inflammatory agents, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1). Administration of tamoxifen following SAH significantly ameliorated the early brain injury (EBI), such as brain edema, blood-brain barrier (BBB) impairment, and clinical behavior scale. Learning deficits induced by SAH were markedly alleviated after tamoxifen treatment.
  
  
  CONCLUSIONS
  Post-SAH tamoxifen administration may attenuate TLR4/NF-kappaB-mediated inflammatory response in the rat brain and result in abatement of the development of EBI and cognitive dysfunction after SAH.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Sun
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Ji
authors.forename: Tong
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China. Dr.Zhongwang@gmail.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D013629:Tamoxifen