Hein Marc, Zoremba Norbert, Bleilevens Chistian, Bruells Christian, Rossaint Rolf, Roehl Anna B
BMC Neurol. 2013 Aug 12;13:106. doi: 10.1186/1471-2377-13-106.
Neuroprotective strategies in ischemic stroke are an important challenge in clinical and experimental research as an adjunct to reperfusion therapy that may reduce neurologic injury and improve outcome. The neuroprotective properties of levosimendan in traumatic brain injury in vitro, transient global brain ischemia and focal spinal cord ischemia suggest the potential for similar effects in transient brain ischemia.
Transient brain ischemia was induced for 60 min by intraluminal occlusion of the middle cerebral artery in 40 male Wistar rats under general anesthesia with s-ketamine and xylazine and with continuous monitoring of their blood pressure and cerebral perfusion. Five minutes before inducing reperfusion, a levosimendan bolus (24 μg kg -1) was administered over a 20 minute period. Infarct size, brain swelling, neurological function and the expression of inflammatory markers were quantified 24 hours after reperfusion.
Although levosimendan limited the infarct size and brain swelling by 40% and 53%, respectively, no effect on neurological outcome or mortality could be demonstrated. Upregulation of tumor necrosis factor α and intercellular adhesion molecule 1 was significantly impeded. Cerebral blood flow during reperfusion was significantly reduced as a consequence of sustained autoregulation.
Levosimendan demonstrated significant neuroprotective properties in a rat model of transient brain ischemia by reducing reperfusion injury.
作为再灌注治疗的辅助手段，缺血性中风的神经保护策略是临床和实验研究中的一项重要挑战，其可能减轻神经损伤并改善预后。左西孟旦在体外创伤性脑损伤、短暂性全脑缺血和局灶性脊髓缺血中具有神经保护特性，提示其在短暂性脑缺血中可能有类似作用。
在氯胺酮和赛拉嗪全身麻醉下，通过大脑中动脉腔内闭塞法，对40只雄性Wistar大鼠诱导60分钟的短暂性脑缺血，并持续监测其血压和脑灌注。在诱导再灌注前5分钟，在20分钟内静脉推注左西孟旦（24μg/kg）。再灌注24小时后，对梗死面积、脑肿胀、神经功能和炎症标志物表达进行定量分析。
尽管左西孟旦分别使梗死面积和脑肿胀减少了40%和53%，但对神经功能结局或死亡率未显示出影响。肿瘤坏死因子α和细胞间黏附分子1的上调受到显著抑制。由于持续的自动调节，再灌注期间的脑血流量显著降低。
在短暂性脑缺血大鼠模型中，左西孟旦通过减轻再灌注损伤表现出显著的神经保护特性。
