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首页> 外文期刊>Brain research >Pravastatin acute neuroprotective effects depend on blood brain barrier integrity in experimental cerebral ischemia
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Pravastatin acute neuroprotective effects depend on blood brain barrier integrity in experimental cerebral ischemia

机译：普伐他汀的急性神经保护作用取决于实验性脑缺血中血脑屏障的完整性

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Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AICT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke. (C) 2015 Elsevier B.V. All rights reserved.
机译：长期以来，据报道他汀类药物在实验性卒中模型中具有急性神经保护作用。然而，就血管内给药后其脑部作用的时机以及血脑屏障（BBB）穿越特性所起的作用而言，仍然需要解决关键问题。我们测试了亲水性他汀类药物（普伐他汀，100 nM）的作用，该物质在生理条件下很难通过血脑屏障。在体外分离的豚鼠脑制剂中，短暂短暂的大脑中动脉阻塞之前或之后90分钟给予普伐他汀。通过电生理和脑血管张力记录，MAP-2免疫组织化学，通过ZO-1 / FITC-白蛋白分析进行BBB评估，AKT和ERK活化以及全细胞抗氧化能力，进行了多模式结果评估。普伐他汀缺血前给药未产生任何明显作用。普伐他汀缺血后给药可显着预防缺血区域的MAP-2免疫反应性丧失，缺血半球ERK磷酸化水平的提高和全细胞抗氧化能力的增强。电生理参数，血管张力和AICT信号均未改变。在所有缺血的大脑中，从缺血发作开始30分钟开始观察到ZO-1片段和FITC白蛋白外渗，表明BBB完整性丧失。我们的发现表明，血管内普伐他汀的快速抗缺血作用高度依赖于卒中后血脑屏障通透性增加。 （C）2015 Elsevier B.V.保留所有权利。

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