Platelet Glycoprotein Ibα is an Important Mediator of Ischemic Stroke in Mice

Overview

Journal Exp Transl Stroke Med

Publisher Biomed Central

Date 2011 Sep 15

PMID 21914206

Citations 18

Authors

Simon F De Meyer

Tobias Schwarz

Daphne Schatzberg

Denisa D Wagner

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Immunothrombosis versus thrombo-inflammation: platelets in cerebrovascular complications.

Li L, Stegner D Res Pract Thromb Haemost. 2024; 8(1):102344.

PMID: 38433977 PMC: 10907225. DOI: 10.1016/j.rpth.2024.102344.

Spatiotemporal profile of neutrophil extracellular trap formation in a mouse model of ischemic stroke.

De Wilde M, Desender L, Tersteeg C, Vanhoorelbeke K, De Meyer S Res Pract Thromb Haemost. 2023; 7(1):100028.

PMID: 36852112 PMC: 9958086. DOI: 10.1016/j.rpth.2022.100028.

Potential Biomarkers of Acute Ischemic Stroke Etiology Revealed by Mass Spectrometry-Based Proteomic Characterization of Formalin-Fixed Paraffin-Embedded Blood Clots.

Rossi R, Mereuta O, Barbachan E Silva M, Gil S, Douglas A, Pandit A Front Neurol. 2022; 13:854846.

PMID: 35518205 PMC: 9062453. DOI: 10.3389/fneur.2022.854846.

Fast clearance of platelets in a commonly used mouse model for GPIbα is impeded by an anti-GPIbβ antibody derivative.

Chen W, Wilson M, Wang Y, Bergmeier W, Lanza F, Li R J Thromb Haemost. 2022; 20(6):1451-1463.

PMID: 35305057 PMC: 9133214. DOI: 10.1111/jth.15702.

Behavioral tests in rodent models of stroke.

Ruan J, Yao Y Brain Hemorrhages. 2021; 1(4):171-184.

PMID: 34322665 PMC: 8315143. DOI: 10.1016/j.hest.2020.09.001.

References

Kleinschnitz C, De Meyer S, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B . Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood. 2009; 113(15):3600-3. DOI: 10.1182/blood-2008-09-180695. View

Murakami K, Kondo T, Epstein C, Chan P . Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice. Stroke. 1997; 28(9):1797-804. DOI: 10.1161/01.str.28.9.1797. View

De Meyer S, Schwarz T, Deckmyn H, Denis C, Nieswandt B, Stoll G . Binding of von Willebrand factor to collagen and glycoprotein Ibalpha, but not to glycoprotein IIb/IIIa, contributes to ischemic stroke in mice--brief report. Arterioscler Thromb Vasc Biol. 2010; 30(10):1949-51. DOI: 10.1161/ATVBAHA.110.208918. View

Kleinschnitz C, Pozgajova M, Pham M, Bendszus M, Nieswandt B, Stoll G . Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation. 2007; 115(17):2323-30. DOI: 10.1161/CIRCULATIONAHA.107.691279. View

De Meyer S, De Maeyer B, Deckmyn H, Vanhoorelbeke K . Von Willebrand factor: drug and drug target. Cardiovasc Hematol Disord Drug Targets. 2009; 9(1):9-20. DOI: 10.2174/187152909787581327. View

Denis C, Methia N, Frenette P, Rayburn H, Hynes R, Wagner D . A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci U S A. 1998; 95(16):9524-9. PMC: 21371. DOI: 10.1073/pnas.95.16.9524. View

Markus H, McCollum C, Imray C, Goulder M, Gilbert J, King A . The von Willebrand inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy: a randomized trial. Stroke. 2011; 42(8):2149-53. DOI: 10.1161/STROKEAHA.111.616649. View

Reiner A, Kumar P, Schwartz S, Longstreth Jr W, Pearce R, Rosendaal F . Genetic variants of platelet glycoprotein receptors and risk of stroke in young women. Stroke. 2000; 31(7):1628-33. DOI: 10.1161/01.str.31.7.1628. View

Baker R, Eikelboom J, Lofthouse E, Staples N, Afshar-Kharghan V, Lopez J . Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood. 2001; 98(1):36-40. DOI: 10.1182/blood.v98.1.36. View

10.

Lopez A, Mathers C, Ezzati M, Jamison D, Murray C . Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006; 367(9524):1747-57. DOI: 10.1016/S0140-6736(06)68770-9. View

11.

De Meyer S, Deckmyn H, Vanhoorelbeke K . von Willebrand factor to the rescue. Blood. 2009; 113(21):5049-57. DOI: 10.1182/blood-2008-10-165621. View

12.

Wieberdink R, van Schie M, Koudstaal P, Hofman A, Witteman J, de Maat M . High von Willebrand factor levels increase the risk of stroke: the Rotterdam study. Stroke. 2010; 41(10):2151-6. DOI: 10.1161/STROKEAHA.110.586289. View

13.

Bederson J, Pitts L, Tsuji M, Nishimura M, Davis R, Bartkowski H . Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986; 17(3):472-6. DOI: 10.1161/01.str.17.3.472. View

14.

De Meyer S, Vandeputte N, Pareyn I, Petrus I, Lenting P, Chuah M . Restoration of plasma von Willebrand factor deficiency is sufficient to correct thrombus formation after gene therapy for severe von Willebrand disease. Arterioscler Thromb Vasc Biol. 2008; 28(9):1621-6. DOI: 10.1161/ATVBAHA.108.168369. View

15.

Clark W, Lessov N, Dixon M, Eckenstein F . Monofilament intraluminal middle cerebral artery occlusion in the mouse. Neurol Res. 1998; 19(6):641-8. DOI: 10.1080/01616412.1997.11740874. View

16.

Stoll G, Kleinschnitz C, Nieswandt B . Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood. 2008; 112(9):3555-62. DOI: 10.1182/blood-2008-04-144758. View

17.

Hankey G, Eikelboom J . Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events. Lancet Neurol. 2010; 9(3):273-84. DOI: 10.1016/S1474-4422(10)70038-7. View

18.

Kanaji T, Russell S, Ware J . Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome. Blood. 2002; 100(6):2102-7. DOI: 10.1182/blood-2002-03-0997. View

19.

Salles I, Feys H, Iserbyt B, De Meyer S, Vanhoorelbeke K, Deckmyn H . Inherited traits affecting platelet function. Blood Rev. 2008; 22(3):155-72. DOI: 10.1016/j.blre.2007.11.002. View

20.

De Meyer S, Vanhoorelbeke K, Ulrichts H, Staelens S, Feys H, Salles I . Development of monoclonal antibodies that inhibit platelet adhesion or aggregation as potential anti-thrombotic drugs. Cardiovasc Hematol Disord Drug Targets. 2006; 6(3):191-207. DOI: 10.2174/187152906778249536. View