Simon F De Meyer, Tobias Schwarz, Daphne Schatzberg, Denisa D Wagner
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引用次数: 34
摘要
背景:血小板在缺血性脑卒中中起重要作用。GPIbα是一种主要的血小板受体,对于血小板粘附血管损伤部位暴露的内皮下基质成分至关重要。方法:采用人白细胞介素4受体(GPIbα/IL4Rα)替代GPIbα细胞外部分的转基因小鼠。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小时的梗死面积。此外,使用改良的Bederson评分对功能结果进行评估。结果:我们发现GPIbα/IL4Rα小鼠的梗死面积明显小于WT小鼠(38.0±6.5 mm3比74.2±8.6 mm3, p < 0.001)。与WT动物相比,GPIbα/IL4Rα小鼠的功能Bederson评分显著提高(1.3±0.4比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在缺血性卒中中的重要作用,提示靶向抑制该受体可能为卒中治疗开辟新的途径。
Platelet glycoprotein Ibα is an important mediator of ischemic stroke in mice.
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.