Blood-brain barrier disruption and matrix metalloproteinase-9 expression during, reperfusion injury - Mechanical versus embolic focal ischemia in spontaneously hypertensive rats
Blood-brain barrier disruption and matrix metalloproteinase-9 expression during, reperfusion injury - Mechanical versus embolic focal ischemia in spontaneously hypertensive rats
复制标题
DOI：
10.1161/01.str.0000033932.34467.97
复制
发表时间：
2002-11-01
期刊：
影响因子：
8.3
通讯作者：
Lo, EH
中科院分区：
文献类型：
--
作者：
Aoki, T;Sumii, T;Lo, EH
背景和目的-大部分脑缺血的实验模型使用机械的闭塞和再灌注方法。然而，机械再灌注与血栓溶解之间的差异可能会影响再灌注损伤概况。在这项研究中，我们比较了大鼠局灶性缺血机械与溶栓再灌注后皮质的血流恢复、血脑屏障（BBB）渗透性和基质金属蛋白酶-9（MMP-9）表达。方法-使用雄性自发性高血压大鼠。机械缺血/再灌注通过使用管腔内细丝闭塞大脑中动脉2小时来实现。溶栓再灌注通过在栓塞性局灶性缺血后2小时给予组织纤溶酶原激活剂来实现。局部皮质血流量监测激光多普勒血流仪。用伊文思蓝染色法测定脑皮层血脑屏障通透性。皮质MMP-9水平进行了评估，zymography和免疫组化。结果-血流恢复在机械再灌注过程中是完整的缺血皮质的中央和周边地区。然而，溶栓后，再灌注是不完全的，只有周围中度恢复。机械再灌注后，血脑屏障通透性主要在缺血皮质的中心区域增加，但在溶栓后，中心和外周区域均增加。总的来说，MMP-9水平较高，栓塞与机械缺血/再灌注后，即使缺血性损伤是相似的，在这两个模型在24 hours. Conclusions，有显着差异的配置文件中的血流恢复，血脑屏障泄漏，MMP-9上调与溶栓后局部缺血再灌注机械。
Background and Purpose-Most experimental models of cerebral ischemia use mechanical methods of occlusion and reperfusion. However, differences between mechanical reperfusion versus clot thrombolysis may influence reperfusion injury profiles. In this study we compared blood flow recovery, blood-brain barrier (BBB) permeability, and matrix metalloproteinase-9 (MMP-9) expression in cortex after mechanical versus thrombolytic reperfusion in rat focal ischemia.Methods-Male spontaneously hypertensive rats were used. Mechanical ischemia/reperfusion was achieved with the use of an intraluminal filament to occlude the middle cerebral artery for 2 hours. Thrombolytic reperfusion was achieved by administering tissue plasminogen activator at 2 hours after embolic focal ischemia. Regional cortical blood flow was monitored by laser-Doppler flowmetry. BBB permeability in cortex was measured by Evans blue dye leakage. Cortical MMP-9 levels were assessed with zymography and immunohistochemistry.Results-Blood flow recovery during mechanical reperfusion was complete in both central and peripheral areas of ischemic cortex. However, after thrombolysis, reperfusion was incomplete, with moderate recovery in the periphery only. BBB permeability was mainly increased in the central regions of the ischemic cortex after mechanical reperfusion but was increased in both central and peripheral areas after thrombolysis. Overall, MMP-9 levels were higher after embolic versus mechanical ischemia/reperfusion, even though ischemic injury was similar in both models at 24 hours.Conclusions-There are significant differences in the profiles of blood flow recovery, BBB leakage, and MMP-9 upregulation in mechanical versus thrombolytic reperfusion after focal ischemia.