Schweighöfer Hanna, Rummel Christoph, Roth Joachim, Rosengarten Bernhard
Department of Neurology, Justus-Liebig-University Giessen, Klinikstr. 33, 35392, Giessen, Germany.
Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen, 35392, Giessen, Germany.
Intensive Care Med Exp. 2016 Dec;4(1):19. doi: 10.1186/s40635-016-0091-4. Epub 2016 Jun 29.
Stimulation of the vagus nerve has modulating, anti-inflammatory effects on the cellular immune response in the blood and the spleen, stabilizing brain function. Here, we aimed to investigate its potential effects on immune-to-brain communication focusing on neurophysiological readouts and leukocyte migration to the brain during severe sepsis-like endotoxemia.
Systemic inflammation was induced by intravenous administration of lipopolysaccharide (LPS; 5 mg/kg). Animals received either no manipulation of the vagus nerve, vagotomy, or vagotomy plus vagus nerve stimulation of the distal trunk. Somatosensory evoked potentials and evoked flow velocity response were measured for 4.5 h as indicators of brain function and neurovascular coupling, respectively. In addition, brain areas with (cortex) and without (hypothalamus) tight blood-brain barrier were studied separately using immunohistochemistry and RT-PCR. Moreover, plasma cytokine and leptin levels were analyzed by ELISA.
LPS induced a decline of both neurophysiological parameters, which was prevented by vagus nerve stimulation. As for peripheral organs, LPS-stimulated neutrophil counts increased in the brain and colocalized in the brain with endothelial intercellular adhesion molecule (ICAM)-1. Interestingly, vagal stimulation reduced this colocalization and decreased nuclear translocation of the brain cell activation marker nuclear factor interleukin 6 (NF-IL6). Furthermore, it reduced the gene expression of inflammatory markers and extravasation signals (IL-6, CXCL-1, ICAM-1) in the hypothalamus but not the cortex linked to a moderate decrease in circulating cytokine levels (interleukin 6, tumor necrosis factor alpha) as well as lower plasma leptin concentration.
Our data suggest beneficial effects of anti-inflammatory vagus nerve stimulation on brain function by reducing the interaction of neurotrophil granulocytes with the brain endothelium as well as attenuating inflammatory responses in brain areas lacking a blood-brain barrier.
刺激迷走神经对血液和脾脏中的细胞免疫反应具有调节、抗炎作用，可稳定脑功能。在此，我们旨在研究其对免疫与脑通讯的潜在影响，重点关注严重脓毒症样内毒素血症期间的神经生理学读数和白细胞向脑内的迁移。
通过静脉注射脂多糖（LPS；5mg/kg）诱导全身炎症。动物分别接受不处理迷走神经、迷走神经切断术或迷走神经切断术加远端迷走神经干刺激。分别测量体感诱发电位和诱发性血流速度反应4.5小时，作为脑功能和神经血管耦合的指标。此外，使用免疫组织化学和逆转录聚合酶链反应分别研究有（皮质）和无（下丘脑）紧密血脑屏障的脑区。此外，通过酶联免疫吸附测定法分析血浆细胞因子和瘦素水平。
LPS导致两种神经生理学参数下降，而迷走神经刺激可预防这种下降。至于外周器官，LPS刺激后脑中中性粒细胞计数增加，并与脑内皮细胞间黏附分子（ICAM）-1共定位。有趣的是，迷走神经刺激减少了这种共定位，并减少了脑细胞活化标志物核因子白细胞介素6（NF-IL6）的核转位。此外，它降低了下丘脑而非皮质中炎症标志物和渗出信号（白细胞介素6、CXCL-1、ICAM-1）的基因表达，这与循环细胞因子水平（白细胞介素6、肿瘤坏死因子α）的适度降低以及血浆瘦素浓度降低有关。
我们的数据表明，抗炎性迷走神经刺激通过减少嗜中性粒细胞与脑内皮的相互作用以及减弱缺乏血脑屏障的脑区的炎症反应，对脑功能具有有益作用。
