Aoki Toshiaki, Sumii Toshihisa, Mori Tatsuro, Wang Xiaoying, Lo Eng H
Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass 02129, USA.
Stroke. 2002 Nov;33(11):2711-7. doi: 10.1161/01.str.0000033932.34467.97.
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.
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.
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.
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.
大多数脑缺血实验模型采用机械性闭塞和再灌注方法。然而，机械性再灌注与血栓溶解之间的差异可能会影响再灌注损伤情况。在本研究中，我们比较了大鼠局灶性缺血后机械性再灌注与溶栓再灌注后皮质的血流恢复、血脑屏障（BBB）通透性及基质金属蛋白酶-9（MMP-9）表达。
使用雄性自发性高血压大鼠。通过腔内插入线栓闭塞大脑中动脉2小时实现机械性缺血/再灌注。在栓塞性局灶性缺血2小时后给予组织型纤溶酶原激活剂实现溶栓再灌注。用激光多普勒血流仪监测局部皮质血流。通过伊文思蓝染料渗漏测量皮质中的BBB通透性。用酶谱法和免疫组织化学法评估皮质MMP-9水平。
在缺血皮质的中央和周边区域，机械性再灌注期间的血流恢复均完全。然而，溶栓后再灌注不完全，仅周边区域有中度恢复。机械性再灌注后，BBB通透性主要在缺血皮质的中央区域增加，而溶栓后中央和周边区域均增加。总体而言，尽管两种模型在24小时时的缺血损伤相似，但栓塞性缺血/再灌注后的MMP-9水平高于机械性缺血/再灌注后的水平。
局灶性缺血后，机械性再灌注与溶栓再灌注在血流恢复、BBB渗漏及MMP-9上调情况方面存在显著差异。
