GPVI‑Fc‑PEG improves cerebral infarct volume and cerebral thrombosis in mouse model with cerebral thrombosis

  • Authors:
    • Yimae Wufuer
    • Xuefeng Shan
    • Magaoweiya Sailike
    • Kamile Adilaimu
    • Songfeng Ma
    • Huguo Wang
  • View Affiliations

  • Published online on: September 20, 2017     https://doi.org/10.3892/mmr.2017.7556
  • Pages: 7561-7568
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Cerebral thrombosis is one of the most common causes of cerebral infarction, and anticoagulation therapy is a routine treatment in patients with hemorrhagic cerebral venous thrombosis. The hemostatic function of platelets is important for the anticoagulation therapy of thrombosis. Glycoprotein VI (GPVI) is reported as the major signaling receptor for collagen and is exclusively expressed on platelets and megakaryocytes, initiating platelet recruitment at sites of vascular injury and demonstrating numerous beneficial effects for patients with cerebral thrombosis. In the present study, thrombus formation and platelet adhesion following endothelial injury was monitored in the jugular vein by intra‑vital fluorescence microscopy. The morphological and clinical observations of cerebral thrombosis were investigated and analyzed in a mouse model with cerebral thrombosis. In addition, the present study investigated the effect of fusion protein GPVI modified with Fc and PEG, which is specifically linked to the extracellular domain of GPVI (GPVI‑Fc‑PEG), on thrombus formation following vessel wall injury and on experimental mice with cerebral thrombosis. The maximum tolerated dose (MTD) was identified as 0.18 mg. GPVI‑Fc‑PEG competitively bound to and prevented von Willebrand Factor‑collagen interactions. The results of the present study demonstrated that cerebral thrombosis was greatly relieved and improved functional outcomes treatment with an MTD of GPVI‑Fc‑PEG following endothelial injury, compared with GPVI‑Fc‑treated mice. In addition, cerebral edema and infarct size was improved compared with GPVI‑Fc‑treated mice with ischemic stroke immediately prior to reperfusion. Furthermore, treatment of GPVI‑Fc‑PEG led to increased reperfusion and improved survival following cerebral thrombosis compared with treatment with either single agent alone. Taken together, GPVI‑Fc‑PEG relieved cerebral thrombosis following ischemic stroke and improved prognostic preclinical outcomes without intracranial bleeding, which suggested that GPVI‑Fc‑PEG may be a potential candidate for cerebral thrombosis therapy.
View Figures
View References

Related Articles

Journal Cover

November-2017
Volume 16 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Wufuer Y, Shan X, Sailike M, Adilaimu K, Ma S and Wang H: GPVI‑Fc‑PEG improves cerebral infarct volume and cerebral thrombosis in mouse model with cerebral thrombosis. Mol Med Rep 16: 7561-7568, 2017
APA
Wufuer, Y., Shan, X., Sailike, M., Adilaimu, K., Ma, S., & Wang, H. (2017). GPVI‑Fc‑PEG improves cerebral infarct volume and cerebral thrombosis in mouse model with cerebral thrombosis. Molecular Medicine Reports, 16, 7561-7568. https://doi.org/10.3892/mmr.2017.7556
MLA
Wufuer, Y., Shan, X., Sailike, M., Adilaimu, K., Ma, S., Wang, H."GPVI‑Fc‑PEG improves cerebral infarct volume and cerebral thrombosis in mouse model with cerebral thrombosis". Molecular Medicine Reports 16.5 (2017): 7561-7568.
Chicago
Wufuer, Y., Shan, X., Sailike, M., Adilaimu, K., Ma, S., Wang, H."GPVI‑Fc‑PEG improves cerebral infarct volume and cerebral thrombosis in mouse model with cerebral thrombosis". Molecular Medicine Reports 16, no. 5 (2017): 7561-7568. https://doi.org/10.3892/mmr.2017.7556