Gutiérrez Aguilar Germán Fernando, Alquisiras-Burgos Iván, Franco-Pérez Javier, Pineda-Ramírez Narayana, Ortiz-Plata Alma, Torres Ismael, Pedraza-Chaverri José, Aguilera Penélope
Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Insurgentes Sur #3877, Mexico City 14269, Mexico.
Laboratorio de Formación Reticular, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Insurgentes Sur #3877, Mexico City 14269, Mexico.
Brain Sci. 2020 Sep 20;10(9):651. doi: 10.3390/brainsci10090651.
Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to oxidative stress and inflammation modulate GLUT3 expression, the purpose of this work was to assess the effect of resveratrol on GLUT3 expression levels after ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by different times of reperfusion. Resveratrol (1.9 mg/kg; i. p.) was administered at the onset of the restoration of the blood flow. Quantitative-PCR and Western blot showed that MCAO provoked a substantial increase in GLUT3 expression in the ipsilateral side to the lesion of the cerebral cortex. Immunofluorescence assays indicated that GLUT3 levels were upregulated in astrocytes. Additionally, an important increase in GLUT3 occurred in other cellular types (e.g., damaged neurons, microglia, or infiltrated macrophages). Immunodetection of the microtubule-associated protein 2 (MAP2) showed that MCAO induced severe damage to the neuronal population. However, the administration of resveratrol at the time of reperfusion resulted in injury reduction. Resveratrol also prevented the MCAO-induced increase of GLUT3 expression. In conclusion, resveratrol protects neurons from damage induced by ischemia and prevents GLUT3 upregulation in the damaged brain that might depend on AMPK activation.
葡萄糖转运蛋白（GLUT）3上调是在脑代谢能量降低时被激活以防止细胞损伤的一种适应性反应。白藜芦醇是一种具有抗氧化和抗炎特性的天然多酚，可保护神经元免受脑缺血诱导的损伤。由于对氧化应激和炎症敏感的转录因子调节GLUT3的表达，因此本研究的目的是评估白藜芦醇对缺血后GLUT3表达水平的影响。雄性Wistar大鼠接受2小时的大脑中动脉闭塞（MCAO），然后进行不同时间的再灌注。在血流恢复开始时给予白藜芦醇（1.9mg/kg；腹腔注射）。定量PCR和蛋白质印迹显示，MCAO引起大脑皮层病变同侧GLUT3表达显著增加。免疫荧光分析表明，星形胶质细胞中GLUT3水平上调。此外，其他细胞类型（如受损神经元、小胶质细胞或浸润巨噬细胞）中GLUT3也有重要增加。微管相关蛋白2（MAP2）的免疫检测显示，MCAO对神经元群体造成严重损伤。然而，在再灌注时给予白藜芦醇可减轻损伤。白藜芦醇还可防止MCAO诱导的GLUT3表达增加。总之，白藜芦醇可保护神经元免受缺血诱导的损伤，并防止受损脑中GLUT3上调，这可能依赖于AMPK激活。
