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

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.

Cerebral blood flow and apoptosis-associated factor with electroacupuncture in a traumatic brain injury rat model.

OBJECTIVE: Electroacupuncture (EA) has been widely used for treatment of stroke, but there is little information on the effect of EA on the neuroprotective function in traumatic brain injury (TBI). The aim of the present study was to investigate the protective effects and mechanisms of EA treatment in a TBI rat model. METHODS: Male Sprague-Dawley rats were randomly divided into four groups: sham operation, TBI control, TBI+EA treated for 30 min or TBI+EA treated for 60 min. The animals were treated with EA immediately after TBI. The EA was applied at acupuncture points GV20, GV26, LI4 and KI1 with a dense-dispersed wave, frequencies of 0.2 and 1 Hz, and amplitude of 1 mA for 30 or 60 min. Regional blood flow, cell infarction volume, extent of neuronal apoptosis, expression of cell apoptosis-associated factor transforming growth-interacting factor (TGIF) were studied, and functional outcome was assessed by running speed test. All tests except regional blood flow were performed 72 h after TBI onset. RESULTS: Immediately after TBI, compared with the TBI control groups, the regional blood flow was significantly increased by EA treatment for 60 min. Compared with the TBI controls 72 h after TBI, the TBI-induced run speed impairment, infarction volume, neuronal apoptosis and apoptosis-associated TGIF expression were significantly improved by EA treatment. CONCLUSIONS: The treatment of TBI in the acute stage with EA for 60 min could increase the regional blood flow and attenuate the levels of TGIF in the injured cortex, might lead to a decrease in neuronal apoptosis and cell infarction volume, and might represent one mechanism by which functional recovery may occur.