RESUMO
OBJECTIVE: 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. MATERIALS AND METHODS: Anesthetized 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. RESULTS: Compared 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. CONCLUSIONS: 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.
