標題: | Extracellular signal-regulated kinase 1/2 is involved in a tamoxifen neuroprotective effect in a lateral fluid percussion injury rat model |
作者: | Tsai, Yin-Tzu Wang, Che-Chuan Leung, Pak-On Lin, Kao-Chang Chio, Chung-Ching Hu, Chiao-Ya Kuo, Jinn-Rung 光電系統研究所 Institute of Photonic System |
關鍵字: | Fluid percussion injury;Tamoxifen;Extracellular signal-regulated kinases (ERK1/2);Cell apoptosis;Infarction volume;Maximal angle |
公開日期: | 1-六月-2014 |
摘要: | 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. Materials and 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. (C) 2014 Elsevier Inc. All rights reserved. |
URI: | http://dx.doi.org/10.1016/j.jss.2014.02.009 http://hdl.handle.net/11536/24186 |
ISSN: | 0022-4804 |
DOI: | 10.1016/j.jss.2014.02.009 |
期刊: | JOURNAL OF SURGICAL RESEARCH |
Volume: | 189 |
Issue: | 1 |
起始頁: | 106 |
結束頁: | 116 |
顯示於類別: | 期刊論文 |