Jean W C, Spellman S R, Nussbaum E S, Low W C
Department of Neurosurgery, University of Minnesota, Minneapolis 55455, USA.
Neurosurgery. 1998 Dec;43(6):1382-96; discussion 1396-7. doi: 10.1097/00006123-199812000-00076.
Recent evidence indicates that thrombolysis may be an effective therapy for the treatment of acute ischemic stroke. However, the reperfusion of ischemic brain comes with a price. In clinical trials, patients treated with thrombolytic therapy have shown a 6% rate of intracerebral hemorrhage, which was balanced against a 30% improvement in functional outcome over controls. Destruction of the microvasculature and extension of the infarct area occur after cerebral reperfusion. We have reviewed the existing data indicating that an inflammatory response occurring after the reestablishment of circulation has a causative role in this reperfusion injury. The recruitment of neutrophils to the area of ischemia, the first step to inflammation, involves the coordinated appearance of multiple proteins. Intercellular adhesion molecule-1 and integrins are adhesion molecules that are up-regulated in endothelial cells and leukocytes. Tumor necrosis factor-alpha, interleukin-1, and platelet-activating factor also participate in leukocyte accumulation and subsequent activation. Therapies that interfere with the functions of these factors have shown promise in reducing reperfusion injury and infarct extension in the experimental setting. They may prove to be useful adjuncts to thrombolytic therapy in the treatment of acute ischemic stroke.
近期证据表明，溶栓可能是治疗急性缺血性卒中的有效疗法。然而，缺血性脑再灌注是有代价的。在临床试验中，接受溶栓治疗的患者出现脑出血的比例为6%，但与对照组相比，其功能结局改善了30%。脑再灌注后会发生微血管破坏和梗死面积扩大。我们回顾了现有数据，这些数据表明循环重建后发生的炎症反应在这种再灌注损伤中起因果作用。中性粒细胞募集到缺血区域是炎症的第一步，这涉及多种蛋白质的协同出现。细胞间黏附分子-1和整合素是在内皮细胞和白细胞中上调的黏附分子。肿瘤坏死因子-α、白细胞介素-1和血小板活化因子也参与白细胞聚集及随后的活化。干扰这些因子功能的疗法在实验环境中已显示出有望减少再灌注损伤和梗死扩展。它们可能被证明是急性缺血性卒中治疗中溶栓治疗的有用辅助手段。
