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Platelet glycoprotein Ibα is an important mediator of ischemic stroke in mice

机译:血小板糖蛋白Ibα是小鼠缺血性中风的重要介质

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Background Platelets play an important role in ischemic stroke. GPIbα is a major platelet receptor that is critical for platelet adhesion to exposed subendothelial matrix components at sites of vascular damage. Methods In this study, we used transgenic mice in which the extracellular part of GPIbα is replaced by human interleukin 4-receptor (GPIbα/IL4Rα). We observed normal brain vasculature in these mice. We compared infarct size in GPIbα/IL4Rα and wild-type (WT) mice 23 hours after 1-hour transient middle cerebral artery occlusion (tMCAO). In addition, the functional outcome was evaluated using a modified Bederson score. Results We found a significantly smaller infarct size in GPIbα/IL4Rα mice compared to WT mice (38.0 ± 6.5 mm3 vs. 74.2 ± 8.6 mm3, p < 0.001). The decrease in infarct size was functionally relevant as indicated by a significantly better functional Bederson score in GPIbα/IL4Rα mice compared to WT animals (1.3 ± 0.4 vs. 2.7 ± 0.3, p < 0.05). Conclusions Our data illustrate and further confirm the important role of platelet GPIbα in ischemic stroke, suggesting that targeted inhibition of this receptor may open new avenues in stroke treatment.
机译:背景血小板在缺血性中风中起重要作用。 GPIbα是一种主要的血小板受体,对于血小板粘附至血管损伤部位暴露的内皮下基质成分至关重要。方法在本研究中,我们使用了转基因小鼠,其中GPIbα的细胞外部分被人白介素4受体(GPIbα/IL4Rα)取代。我们在这些小鼠中观察到正常的脑血管。我们比较了GPIbα/IL4Rα和野生型(WT)小鼠在1小时短暂性大脑中动脉闭塞(tMCAO)后23小时的梗塞面积。此外,使用改良的Bederson评分评估功能结局。结果我们发现,与WT小鼠相比,GPIbα/IL4Rα小鼠的梗死面积明显较小(38.0±6.5 mm3对74.2±8.6 mm3,p <0.001)。与WT动物相比,GPIbα/IL4Rα小鼠的功能性Bederson评分明显更好(1.3±0.4 vs. 2.7±0.3,p <0.05),表明梗死面积的减少与功能相关。结论我们的数据说明并进一步证实了血小板GPIbα在缺血性中风中的重要作用,这表明该受体的靶向抑制作用可能为中风治疗开辟新途径。

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