Mouse model of microembolic stroke and reperfusion
Mouse model of microembolic stroke and reperfusion
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DOI：
10.1161/01.str.0000137412.35700.0e
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发表时间：
2004-09-01
期刊：
影响因子：
8.3
通讯作者：
Muzykantov, VR
中科院分区：
文献类型：
--
作者：
Atochin, DN;Murciano, JC;Muzykantov, VR
背景和目的-为了检测纤维蛋白溶解在中风中的作用，我们使用了一种小鼠模型，在该模型中，预先形成的直径为2.5- 3 μ m的纤维蛋白微栓子被注射到脑循环中。微栓子在下游的毛细血管前血管系统和易受fibrinolysation.Methods -我们注射不同剂量的微栓子到小鼠的颈内动脉和其分布特点，对脑血流量，神经功能缺损，梗死面积和自发溶解的影响。通过比较野生型和组织型纤溶酶原激活物（tPA）基因敲除（tPA（-/-））小鼠，我们分析了内源性tPA在急性血栓性stroke.Results中的作用-微栓子引起剂量依赖性脑损伤。虽然中等剂量的微栓子随后自发再灌注，但它们导致可再现的损伤。基因敲除tPA显着延迟溶解的脑栓塞和恢复的血流和enaberates缺血性血栓性梗死在brain.Conclusions -我们描述了一种微栓塞模型中风，其中损伤程度可以控制注射的微栓子的剂量。与血管闭塞模型不同，该模型可以被调节以允许自发的纤维蛋白溶解。应用于tPA（-/-）小鼠支持内源性tPA在血栓形成后恢复脑血流和限制梗死面积中的关键作用。
Background and Purpose - To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-mum-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis.Methods - We injected various doses of microemboli into the internal carotid artery in mice and characterized their distribution, effects on cerebral blood flow, neurological deficit, infarct area, and spontaneous dissolution. By comparing wild-type and tissue plasminogen activator (tPA) knockout (tPA(-/-)) mice, we analyzed the role of endogenous tPA in acute thrombotic stroke.Results - Microemboli cause dose-dependent brain injury. Although moderate doses of microemboli are followed by spontaneous reperfusion, they result in reproducible injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and restoration of blood flow and aggravates ischemic thrombotic infarction in the brain.Conclusions - We describe a microembolic model of stroke, in which degree of injury can be controlled by the dose of microemboli injected. Unlike vessel occlusion models, this model can be modulated to allow spontaneous fibrinolysis. Application to tPA(-/-) mice supports a key role of endogenous tPA in restoring cerebral blood flow and limiting infarct size after thrombosis.