From the Institute of Anaesthesiology, University Hospital Zurich (BBS, LB, TR, PE, MH, MS), Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland (BBS, LB, TR, CB, MS); and Department of Anaesthesiology, University of Illinois at Chicago, Chicago, Illinois, USA (BBS) *Beatrice Beck-Schimmer and Lukas Baumann contributed equally as first authors.
Eur J Anaesthesiol. 2017 Nov;34(11):764-775. doi: 10.1097/EJA.0000000000000668.
Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics.
We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes.
Laboratory rat study.
Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016.
A total of 32 adult male Wistar rats.
After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg h) or sevoflurane (2 vol%) continuously for 12 h.
Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined.
Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P < 0.001). There was no significant difference in microglia or astrocyte activation or apoptosis in the brain between sevoflurane and propofol.
We have shown that systemic attenuation of inflammation by the volatile anaesthetic sevoflurane did not translate into attenuated neuro-inflammation in this LPS-induced inflammation model.
Animal approval No. 134/2014, Veterinäramt Zürich.
据信，败血性脑病是由内毒素（如脂多糖[LPS]）引发的神经炎症引起的。免疫系统的调节是挥发性麻醉剂的特性。
我们旨在研究 LPS 诱导的脓毒症大鼠模型中的全身和脑炎症反应。我们比较了两种不同的镇静策略，即静脉注射异丙酚和挥发性麻醉剂七氟醚，假设后者可能减轻神经炎症过程。
实验室大鼠研究。
苏黎世大学医院和苏黎世大学 Irchel 的基础研究实验室，2014 年 8 月至 2016 年 6 月。
共 32 只成年雄性 Wistar 大鼠。
在气管切开和机械通气后，使用静脉内 LPS 或磷酸盐缓冲盐水作为对照诱导脓毒症之前，对麻醉大鼠进行监测。大鼠用异丙酚（10mg/kg/h）或七氟醚（2 体积%）连续镇静 12 小时。
测定细胞因子诱导的中性粒细胞趋化因子 1、单核细胞趋化蛋白 1 和 IL-6 等全身炎症标志物。脑组织中也测定了相同的细胞因子。用髓过氧化物酶定义中性粒细胞积聚，用离子钙结合衔接分子-1 定义小胶质细胞激活，用胶质纤维酸性蛋白定义星形胶质细胞激活，从而评估脑内细胞反应。最后，确定脑损伤。
用 LPS 处理的两种镇静组动物的血流动力学均稳定。七氟醚-LPS 动物的血液细胞因子峰值较低。在 LPS 动物的脑组织中，趋化因子 1 是唯一明显增加的细胞因子（P=0.003），但异丙酚和七氟醚之间无差异。在 LPS 攻击后，观察到中性粒细胞在大脑中的积聚。用 LPS 处理的动物的海马体中，小胶质细胞激活明显（P=0.006）。LPS 诱导了明显的星形胶质细胞增生（P<0.001）。在七氟醚和异丙酚之间，脑内小胶质细胞或星形胶质细胞激活或细胞凋亡无显著差异。
我们已经表明，挥发性麻醉剂七氟醚对全身炎症的抑制并不能转化为这种 LPS 诱导的炎症模型中神经炎症的减轻。
动物批准号 134/2014，苏黎世兽医局。
