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. 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.