Rauen Katrin, Pop Viorela, Trabold Raimund, Badaut Jerome, Plesnila Nikolaus
Laboratory of Experimental Neurosurgery, Department of Neurosurgery & Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center, Munich, Germany.
J Neurotrauma. 2020 Feb 15;37(4):665-674. doi: 10.1089/neu.2019.6653. Epub 2019 Dec 4.
Brain edema formation contributes to secondary brain damage and unfavorable outcome after traumatic brain injury (TBI). Aquaporins (AQP), highly selective water channels, are involved in the formation of post-trauma brain edema; however, their regulation is largely unknown. Because vasopressin receptors are involved in AQP-mediated water transport in the kidney and inhibition of V receptors reduces post-trauma brain edema formation, we hypothesize that cerebral AQPs may be regulated by V receptors. Cerebral and messenger ribonucleic acid (mRNA) and AQP1 and AQP4 protein levels were quantified in wild-type and V receptor knockout mice before and 15 min, 1, 3, 6, 12, or 24 h after experimental TBI by controlled cortical impact. In non-traumatized mice, we found AQP1 and AQP4 expression in cortical neurons and astrocytes, respectively. Experimental TBI had no effect on mRNA or AQP4 protein expression, but increased mRNA ( < 0.05) and AQP1 protein expression ( < 0.05) in both hemispheres. The mRNA and AQP1 protein regulation was blunted in V receptor knockout mice. The V receptors regulate cerebral AQP1 expression after experimental TBI, thereby unraveling the molecular mechanism by which these receptors may mediate brain edema formation after TBI.
脑水肿的形成会导致创伤性脑损伤（TBI）后的继发性脑损伤和不良预后。水通道蛋白（AQP）是高度选择性的水通道，参与创伤后脑水肿的形成；然而，其调节机制在很大程度上尚不清楚。由于血管加压素受体参与肾脏中AQP介导的水转运，并且抑制V受体可减少创伤后脑水肿的形成，我们推测脑AQP可能受V受体调节。通过控制性皮质撞击对野生型和V受体基因敲除小鼠进行实验性TBI，在伤前以及伤后15分钟、1小时、3小时、6小时、12小时或24小时，对大脑中的和信使核糖核酸（mRNA）以及AQP1和AQP4蛋白水平进行定量分析。在未受伤的小鼠中，我们分别在皮质神经元和星形胶质细胞中发现了AQP1和AQP4的表达。实验性TBI对mRNA或AQP4蛋白表达没有影响，但在双侧半球中增加了mRNA（<0.05）和AQP1蛋白表达（<0.05）。在V受体基因敲除小鼠中，mRNA和AQP1蛋白的调节作用减弱。V受体在实验性TBI后调节脑AQP1的表达，从而揭示了这些受体可能介导TBI后脑水肿形成的分子机制。
