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

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

World Neurosurg. 2018 Jan 15;:

Authors: Lim SW, Eric Nyam TT, Hu CY, Chio CC, Wang CC, Kuo JR

Abstract
PURPOSE: The aim of the present study is to 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.
MATERIAL AND METHODS: Anesthetized male Sprague-Dawley rats were divided into four 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 was also investigated by western blotting, and ERα expression in neurons, microglia and astroglia were each detected using immunofluorescence staining. Neuronal apoptosis (maker Caspase-3), activated microglia (maker Ox42), astroglia (maker GFAP), and tumor necrosis factor-alpha (TNF-α) expression in microglia and astroglia in the cortex were evaluated by immunofluorescence staining methods.
RESULTS: Compared to sham-operated controls, the TBI-induced proprioception inhibition was significantly attenuated by TMX therapy on day 3 after TBI. Using immunofluorescence staining, the TBI-induced neuronal loss, apoptosis, activated microglia and astrocyte expression TNF-α and ERα in the cortex were significantly reduced by tamoxifen therapy.
CONCLUSION: Our 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.

PMID: 29353027 [PubMed - as supplied by publisher]

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