Comparative Analysis of Different Methods of Ischemia/Reperfusion in Hyperglycemic Stroke Outcomes: Interaction with tPA.
Comparative Analysis of Different Methods of Ischemia/Reperfusion in Hyperglycemic Stroke Outcomes: Interaction with tPA.
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DOI：
10.1007/s12975-015-0391-0
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发表时间：
2015-06
影响因子：
6.9
通讯作者：
Ergul, Adviye
中科院分区：
文献类型：
--
作者：
Hafez, Sherif;Hoda, Md Nasrul;Guo, Xinyue;Johnson, Maribeth H.;Fagan, Susan C.;Ergul, Adviye
关键词：
急性高血糖（HG）可加重再灌注损伤，加重tPA诱导的出血性转化（HT）。先前的实验性高血糖卒中研究采用非常高的血糖水平，并仅使用缝线闭塞模型诱导缺血。只有少数研究评估了HG在栓塞性卒中中的作用，并且大多涉及使用比患者使用的剂量高10倍的tPA。然而，急性HG和低（人）剂量tPA之间的相互作用，在不同的实验模型的中风从来没有报道。我们首先测试了急性HG的严重程度对卒中结局的影响。基于我们的研究结果，我们比较了轻度急性HG对大鼠神经血管损伤的影响，这些大鼠在使用和不使用低剂量tPA的情况下进行了缝合或血栓栓塞性闭塞。我们评估了脑血流量、神经行为结果、梗死、出血和水肿。与无tPA组相比，tPA未改变对照组或高血糖动物的梗死面积。在缝合和栓塞闭塞模型中，HG增加HT并恶化功能结局。在两种模型中，HG和tPA的组合加重了血管损伤，并使神经功能缺损恶化。我们的研究结果表明，HG和低剂量tPA之间的相互作用对血管系统和功能结局具有不利影响，与再灌注方法无关。
Acute hyperglycemia (HG) exacerbates reperfusion injury and aggravates tPA-induced hemorrhagic transformation (HT). Previous experimental hyperglycemic stroke studies employed very high blood glucose levels and exclusively used suture occlusion model to induce ischemia. Only few studies evaluated HG in embolic stroke and mostly involving the use of 10-fold higher dose of tPA than that is used in patients. However, the interaction between acute HG and low (human) dose tPA in different experimental models of stroke has never been reported. We first tested the impact of the severity of acute HG on stroke outcome. Building upon our findings, we then compared the impact of mild acute HG on neurovascular injury in rats subjected to suture or thromboembolic occlusion with and without low dose tPA. We assessed cerebral blood flow, neurobehavioral outcomes, infarction, hemorrhage and edema. tPA did not change the infarct size in either control or hyperglycemic animals when compared to no tPA groups. HG increased HT and worsened functional outcomes in both suture and embolic occlusion models. The combination of HG and tPA exacerbated the vascular injury and worsened the neurological deficits more than each individual treatment in both models. Our findings show that the interaction between HG and even low dose tPA has detrimental effects on the cerebrovasculature and functional outcomes independent of the method of reperfusion.
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影响因子：
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