RESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms.</p><p><b>METHODS</b>Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR.</p><p><b>RESULTS</b>All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.</p><p><b>CONCLUSION</b>Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.</p>
Asunto(s)
Animales , Masculino , Ratones , Traumatismos por Explosión , Lesiones Traumáticas del Encéfalo , Cafeína , Farmacología , Corteza Cerebral , Patología , Hipocampo , Patología , Trastornos de la Memoria , Ratones Endogámicos C57BL , ARN Mensajero , Receptor de Adenosina A1 , GenéticaRESUMEN
Explosive blast injury has become the most prevalent injury in recent military conflicts and terrorist attacks. The magnitude of this kind of polytrauma is complex due to the basic physics of blast and the surrounding environments. Therefore, development of stable, reproducible and controllable animal model using an ideal blast simulation device is the key of blast injury research. The present review addresses the modeling of blast injury and applications of shock tubes.
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Animales , Traumatismos por Explosión , Modelos Animales de Enfermedad , Ondas de Choque de Alta Energía , InvestigaciónRESUMEN
<p><b>OBJECTIVE</b>To study the role of Smad3 in transforming growth factor-beta1 (TGF-beta1)-induced bi-directional effects on skin fibroblast proliferation.</p><p><b>METHODS</b>The Smad3 small interfering (siRNA) plasmid was constructed using a pSUPER vector. The efficiency of cell transfection was detected by fluorescence microscopy, and the inhibitory effect of the plasmid was assessed by real-time quantitative RT-PCR and immunohistochemistry. The effect of the plasmid on the fibroblast proliferation and Smad3 binding activity was analyzed by BRDU ELISA and EMSA, respectively.</p><p><b>RESULTS</b>The transfection efficiency of the plasmid into the cells was 41.2%. The Smad3 siRNA plasmid produced efficient and specific inhibition of the expression of Smad3, and promoted the cell proliferation in a dose-dependent manner and abrogated the bi-directional effect of TGF-beta1 on the cell proliferation and Smad3 binding activity.</p><p><b>CONCLUSION</b>The siRNA targeting Smad3 gene can inhibit the protein expression and RNA transcription of Smad3, and TGF-beta1 exerts bi-directional regulation on fibroblast proliferation by modulating Smad3 activity.</p>
Asunto(s)
Animales , Ratas , Proliferación Celular , Células Cultivadas , Fibroblastos , Biología Celular , Interferencia de ARN , ARN Interferente Pequeño , Genética , Ratas Wistar , Piel , Biología Celular , Proteína smad3 , Genética , Transfección , Factor de Crecimiento Transformador beta1 , FarmacologíaRESUMEN
The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, on impairment in a cortical impact model of traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms. Mice were injected (i.p.) with saline, 1 mg/kg (S)-4C3HPG, 5 mg/kg (S)-4C3HPG and 10 mg/kg (S)-4C3HPG (n=10 per group), respectively, at 30 min before moderate TBI. Neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA in injured cortex were also detected by real-time RT-PCR. The results showed that the neurological deficits and cerebral edema were significantly attenuated in mice pretreated with (S)-4C3HPG (5 and 10 mg/kg respectively) compared with those in mice pretreated with saline. Furthermore, (S)-4C3HPG treatment also decreased the glutamate concentration in CSF and the expressions of TNF-α and IL-1β mRNA remarkably in a dose-dependent manner. These results suggest that (S)-4C3HPG treatment attenuates cortical impact-induced brain injury possibly via suppression of glutamate release and inhibition of excessive inflammatory cytokine production. These findings highlight the potential benefit of glutamate metabotropic receptor ligand for preventing TBI.