• World Neurosurg · Apr 2018

    Estrogen Receptor-α is Involved in Tamoxifen Neuroprotective Effects in a Traumatic Brain Injury Male Rat Model.

    • Sher-Wei Lim, Eric Nyam Tt, Cho-Ya Hu, Chung-Ching Chio, Che-Chuan Wang, and Jinn-Rung Kuo.
    • Department of Neurosurgery, Chia-Li Chi-Mei Medical Center, Tainan, Taiwan; Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan.
    • World Neurosurg. 2018 Apr 1; 112: e278-e287.

    ObjectiveTo determine the neuroprotective mechanisms of tamoxifen (TMX) during traumatic brain injury (TBI), especially the effects on estrogen receptor-α (ERα) expression, as well as neuroinflammatory associations.Materials And MethodsAnesthetized male Sprague-Dawley rats were divided into 4 groups: sham-operated controls, sham-operated controls given TMX (1 mg/kg/per day) for 3 days, those given a vehicle solution immediately after TBI, and those given TMX (1 mg/kg/per day) for 3 days. The functional outcome was evaluated by assessments of body weight and proprioception. The total ERα expression in the cortex also was investigated by Western blotting, and ERα expression in neurons, microglia, and astroglia were each detected via immunofluorescence staining. Neuronal apoptosis (marker caspase-3), activated microglia (marker OX42), astroglia (marker glial fibrillary acidic protein), and tumor necrosis factor-alpha expression in microglia and astroglia in the cortex were evaluated by immunofluorescence staining methods.ResultsCompared with sham-operated controls, the TBI-induced proprioception inhibition was significantly attenuated by TMX therapy on day 3 after TBI. Using immunofluorescence staining, we found that the TBI-induced neuronal loss, apoptosis, activated microglia, and astrocyte expression and tumor necrosis factor-alpha and ERα in the cortex were significantly reduced by TMX therapy.ConclusionsOur results suggest that the intraperitoneal injection of TMX (1 mg/kg/per day) for 3 days may affect ERα expression in neurons and glia, which is accompanied by neuroinflammation and neuronal apoptosis, and it might represent one mechanism by which functional recovery occurs. We consider TMX administration to be a promising strategy for TBI.Copyright © 2018 Elsevier Inc. All rights reserved.

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