Why the study?
Does genetic replacement of platelet GPIbα reduce infarct size and improve functional outcome in a mouse model of ischemic stroke?
Does genetic replacement of platelet GPIbα reduce infarct size and improve functional outcome in a mouse model of ischemic stroke?
Genetic deletion of the extracellular domain of platelet GPIbα significantly reduces infarct size and improves functional outcome in a mouse model of ischemic stroke, highlighting it as a potential therapeutic target.
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Hypothesis-generating for GPIbα-targeted therapy in ischemic stroke; prospective human studies needed.
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.
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Meyer et al. (2011) studied this question.
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