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首页> 外文期刊>Translational Stroke Research >Neuregulin-1 Effects on Endothelial and Blood–Brain Barrier Permeability After Experimental Injury
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Neuregulin-1 Effects on Endothelial and Blood–Brain Barrier Permeability After Experimental Injury

机译：神经调节蛋白1对实验性损伤后内皮和血脑屏障通透性的影响

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摘要

Blood–brain barrier (BBB) disruption occurs with a high incidence after traumatic brain injury, and is an important contributor to many pathological processes, including brain edema, inflammation, and neuronal cell death. Therefore, BBB integrity is an important potential therapeutic target in the treatment of the acute phase of brain trauma. In this short communication, we report our data showing that neuregulin-1 (NRG1), a growth factor with diverse functions in the central nervous system (CNS), ameliorates pathological increases in endothelial permeability and in BBB permeability in experimental models of injury. For in vitro studies, rat brain endothelial cells were incubated with the inflammatory cytokine IL-1β, which caused an increase in permeability of the cell layer. Co-incubation with NRG1 ameliorated this permeability increase. For in vivo studies, C57Bl/6 mice were subjected to controlled cortical impact (CCI) under anesthesia, and BBB permeability was assessed by measuring the amount of Evans blue dye extravasation at 2 h. NRG1 administered by tail-vein injection 10 min after CCI resulted in a decrease in Evans blue dye extravasation by 35 %. Since Evans blue extravasation may result from an increase in BBB permeability or from bleeding due to trauma, hemoglobin ELISA was also performed at the same time point. There was a trend toward lower levels of hemoglobin extravasation in the NRG1 group, but the results did not reach statistical significance. MMP-9 activity was not different between groups at 2 h. These data suggest that NRG1 has beneficial effects on endothelial permeability and BBB permeability following experimental trauma, and may have neuroprotective potential during CNS injury.
机译：脑外伤后血脑屏障（BBB）破坏发生率很高，并且是许多病理过程的重要因素，包括脑水肿，炎症和神经元细胞死亡。因此，BBB完整性是治疗脑外伤急性期的重要潜在治疗靶标。在这段简短的交流中，我们报告了数据，表明神经调节蛋白1（NRG1）是一种在中枢神经系统（CNS）中具有多种功能的生长因子，可改善损伤实验模型中内皮通透性和BBB通透性的病理性增加。为了进行体外研究，将大鼠脑内皮细胞与炎性细胞因子IL-1β孵育，这导致细胞层的通透性增加。与NRG1共同孵育可改善这种通透性增加。为了进行体内研究，在麻醉下对C57Bl / 6小鼠进行受控的皮层撞击（CCI），并通过在2小时时测量Evans蓝染料外渗量来评估BBB的通透性。在CCI后10分钟通过尾静脉注射NRG1导致伊文思蓝染料外渗减少了35％。由于伊文思蓝外渗可能是由于血脑屏障通透性增加或由于外伤引起的出血而引起的，因此还同时进行了血红蛋白ELISA。 NRG1组有降低血红蛋白外渗的趋势，但结果未达到统计学意义。各组之间2小时的MMP-9活性没有差异。这些数据表明，NRG1对实验性创伤后的内皮通透性和BBB通透性具有有益作用，并且在CNS损伤期间可能具有神经保护作用。

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  • 来源
    《Translational Stroke Research》 |2012年第s1期|119-124|共6页
  • 作者

    Josephine Lok; Song Zhao; Wendy Leung; Ji Hae Seo; Deepti Navaratna; Xiaoying Wang; Michael J. Whalen; Eng H. Lo;

  • 作者单位

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

    Department of Pediatrics Pediatric Critical Care Medicine Massachusetts General Hospital Harvard Medical School Boston MA USA;

    Neuroprotection Research Laboratory Massachusetts General Hospital Harvard Medical School Charlestown MA USA;

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  • 正文语种 eng
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  • 关键词

    Neuregulin-1; Endothelial; Blood–brain barrier; Brain trauma; IL-1β; Permeability;

    机译：神经调节蛋白-1;内皮细胞;血脑屏障;脑外伤;IL-1β;通透性;抗炎性;

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