Skip to main content

Advertisement

Log in

Von Willebrand Factor Activity in Rats after Transient Cerebral Ischemia

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

One of the leading risk factors for recurrent cerebrovascular accidents after cerebral ischemia is dysfunction of the vascular endothelium. Von Willebrand factor (vWF) is a widely recognized marker for endothelial dysfunction associated with imbalance of the release of endothelial substances with procoagulant activity. vWF activity and the hematocrit were studied in Wistar rats after cerebral ischemia induced by 12-min occlusion of both carotid arteries with simultaneous hypotension (45 ± 2 mmHg). Postischemic changes were evaluated in five groups of rats: at 1 h and on days 3, 7, 14, and 21 after ischemia/reperfusion (I/R). Controls consisted of Wistar rats subjected to the same procedure but without ligation of the carotid arteries and hypotension. An increase in vWF activity was seen at 1 h after I/R. By day 3 of the postischemic period, the plasma vWF concentration decreased, which was evidenced by a decrease in the hematocrit to be due to hemodilution. There was a sharp increase in marker activity at postischemia day 7. vWF activity then decreased, reaching the level in control rats by day 21 after I/R. These data provide evidence that single 12-min episodes of I/R of the brain lead to the development of vascular endothelial dysfunction associated with imbalance in the release of endothelial substances with procoagulant activity, which persisted for 14 days after ischemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. I. A. Gonchar, Yu. I. Stepanova, and I. S. Prudyvus, Biochemical Predictors and Markers of Ischemic Stroke, V. S. Kamyshnikov (ed.), Medical Academy of Postgraduate Education, Minsk (2013).

  2. F. Denorme and S. F. De Meyer, “The VWF-GPIb axis in ischaemic stroke: lessons from animal models,” J. Thromb. Haemost., 116, No. 04, 597–604 (2016), https://doi.org/10.1160/TH16-01-0036.

    Article  Google Scholar 

  3. M. M. Khan, D. G. Motto, S. R. Lentz, and A. K. Chauhan, “ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice,” J. Thromb. Haemost., 10, No. 8, 1665–1671 (2012), https://doi.org/10.1111/j.1538-7836.2012.04822.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. N. Dhanesha, P. Prakash, P. Doddapattar, et al., “Endothelial cell-derived von Willebrand factor is the major determinant that mediates von Willebrand factor-dependent acute ischemic stroke by promoting postischemic thrombo-infl ammation,” Arterioscler. Thromb. Vasc. Biol., 36, No. 9, 1829–1837 (2016), https://doi.org/10.1161/ATVBAHA.116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Z. A. Suslina, M. M. Tanashyan, M. A. Domashenko, et al., “Endothelial dysfunction in patients with ischemic stroke,” Ann. Klin. Eksperim. Nevrol., 2, No. 1, 4–11 (2008).

    Google Scholar 

  6. R. J. Esper, R. A. Nordaby, J. O. Vilarico, et al., “Endothelial dysfunction: a comprehensive appraisal,” Cardiovasc. Diabetol., 5, 4–21 (2006); PMCID: PMC143472716504104, https://doi.org/10.1186/1475-2840-5-4.

  7. O. L. Polonetskii and L. Z. Polonetskii, “Endothelial dysfunction and atherosclerosis,” Med. Novosti, 6, 6–11 (2012).

    Google Scholar 

  8. A. V. Voronkov, D. I. Pozdnyakov, and A. V. Mamleev, “Studies of the vasodilatory and antithrombotic functions of the rat cerebral vascular endothelium in various models of its ischemic damage,” Sovrem. Prob. Nauki Obrazovan., No. 5 (2015), http://science-education.ru/ru/article/view?id=22406.

  9. V. N. Shuvaeva, O. P. Gorshkova, and D. P. Dvoretskii, “Coagulation hemostasis in Wistar rats after short-term transient cerebral ischemia,” Ros. Fiziol. Zh., 105, No. 9, 1189–1196 (2019).

    Article  Google Scholar 

  10. F. Arba, A. Giannini, B. Piccardi, et al., “Small vessel disease and biomarkers of endothelial dysfunction after ischaemic stroke,” Eur. Stroke J., 4, No. 2, 119–126 (2019), https://doi.org/10.1177/2396987318805905.

    Article  PubMed  Google Scholar 

  11. A. Poggesi, P. Marco, P. Francesca, et al., “Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review,” J. Cereb. Blood Flow Metab., 36, No. 1, 72–94 (2016), https://doi.org/10.1038/jcbfm.2015.116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. S. A. Povzun, The Major Syndromes: Pathogenesis and Pathological Anatomy, IPK KOSTA. St. Petersburg (2009).

    Google Scholar 

  13. B. Horváth, D. Hegedüs, L. Szapáry, et al., “Investigation of von Willebrand-factor as a marker of endothelial dysfunction in atherosclerotic patients,” Orv. Hetil., 144, No. 50, 2471–2476 (2003).

    PubMed  Google Scholar 

  14. A. V. Babichev, “The role of the endothelium in the mechanisms of hemostasis,” Pediatr., IV, No. 1, 122–127 (2013).

    Google Scholar 

  15. M. A. Reldy, M. Chopek, S. Chao, et al., “Injury induces increase of von Willebrand factor in rat endothelial cells,” Am. J. Pathol., 134, No. 4, 857–864 (1989).

    Google Scholar 

  16. M. L. Smith, G. Bendek, N. Dahlgren, et al., “Models for studying long-term recovery following forebrain ischemia in the rat: 2. A 2-vessel occlusion model,” Acta Neurol. Scand., 69, 385–401 (1984).

    Article  CAS  Google Scholar 

  17. E. P. Kosobyan, I. R. Yarek-Martynova, A. N. Yasamanova, et al., “The role of endothelial dysfunction in the development of cerebrovascular disease in patients with diabetes mellitus,” Sakhar. Diabet, 1, 42–48 (2012).

    Article  Google Scholar 

  18. O. P. Gorshkova, M. V. Lentsman, A. I. Artem’eva, and D. P. Dvoretskii, “Dynamics of pial vessel reactivity after transient cerebral ischemia,” Regionarn. Krovoobrash. Mikrotsirkul., 14, No. 1, 74–78 (2015).

    Google Scholar 

  19. Zh. A. Chubukov, “Von Willebrand factor and endothelial dysfunction in stress,” Prob. Zdorov. Ekol., 2, No. 32, 40–45 (2012).

    Google Scholar 

  20. V. V. Dmitriev, Practical Issues in Clinical Coagulology, Belarus Science, Minsk (2017), ISBN: 978-985-08-2158-4.

    Google Scholar 

  21. H. Q. Yao, F. J. Wang, and Z. Kang, “Effects of endovascular interventions on vWF and Fb levels in type 2 diabetic patients with peripheral artery disease,” Ann. Vasc. Surg., 33, 159–66 (2016), https://doi.org/10.1016/j.avsg.2015.11.018.

    Article  PubMed  Google Scholar 

  22. O. P. Gorshkova and V. N. Shuvaeva, “Dynamics of post-ischemic microcirculatory changes in the rat cerebral cortex rat,” Ros. Fiziol. Zh., 103, No. 8, 866–872 (2017).

    Google Scholar 

  23. Y. Onetti, A. P. Dantas, B. Pirez, et al., “Middle cerebral artery remodeling following transient brain ischemia is linked to early postischemic hyperemia: a target of uric acid treatment,” Am. J. Physiol. Heart Circ. Physiol., 308, No. 8, H862–H874 (2015), https://doi.org/10.1152/ajpheart.0000.2015.

    Article  CAS  PubMed  Google Scholar 

  24. V. I. Skvortsova, “Ischemic stroke: the pathogenesis of ischemia and therapeutic approaches,” Nevrol. Zh., 6, No. 3, 4–9 (2001).

    Google Scholar 

  25. A. Ceulemans, T. Zgavc, R. Kooijman, et al., “The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia,” J. Neuroinflammation, 7, 74 (2010), https://doi.org/10.1186/1742-2094-7-74.

  26. T. Skaria, E. Bachli, and G. Schoedon, “RSPO3 impairs barrier function of human vascular endothelial monolayers and synergizes with pro-inflammatory IL-1,” Mol. Med., 24, No. 1, 45–51 (2018), https://doi.org/10.1186/s10020-018-0048-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. L. Claesson-Welsh, “Vascular permeability – the essentials,” Ups. J. Med. Sci., 120, No. 3, 135–143 (2015), https://doi.org/10.3109/03009734.2015.1064501.

    Article  PubMed  PubMed Central  Google Scholar 

  28. T. N. Yudakova, A. O. Girsh, S. V. Maksimishin, and O. A. Mal’kov, “Correlation of cardiovascular system parameters and endothelial dysfunction in patients with hemorrhagic shock,” Anesteziol. Reanimatol., 6, 11–13 (2013).

    Google Scholar 

  29. O. P. Gorshkova, V. N. Shuvaeva, M. V. Lentsman, and A. I. Artem’eva, “Postischemic changes in the vasomotor function of the endothelium,” Sovrem. Prob. Nauki Obraz., No. 5 (2016), http://www.science-education.ru/ru/article/view?id=25270.

  30. C. J. Boos, B. Balakrishnan, A. D. Blann, and G. Y. Lip, “The relationship of circulating endothelial cells to plasma indices of endothelial damage/dysfunction and apoptosis in acute coronary syndromes: implications for prognosis,” J. Thromb. Haemost., 6, No. 11, 1841–1850 (2008), https://doi.org/10.1111/j.1538-7836.2008.03148.x.

    Article  CAS  PubMed  Google Scholar 

  31. X. Zhu, Y. Cao, L. Wei, et al., “Von Willebrand factor contributes to poor outcome in a mouse model of intracerebral haemorrhage,” Sci. Rep., 6, 35901–35911 (2016), https://doi.org/10.1038/srep35901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. R. Flaumenhaft, “Protein disulfi de isomerase as an antithrombotic target,” Trends Cardiovasc. Med., 23, 264–268 (2013), https://doi.org/10.1016/j.tcm.2013.03.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Y. Wang, “A study of plasma von Willebrand factor concentration in patients with cerebrovascular disease,” Zhonghua Shen Jing Jing Shen Ke Za Zhi, 25, No. 2, 106–108 (1992).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. N. Shuvaeva.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 106, No. 8, pp. 964–973, August, 2020.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shuvaeva, V.N., Gorshkova, O.P. Von Willebrand Factor Activity in Rats after Transient Cerebral Ischemia. Neurosci Behav Physi 51, 496–500 (2021). https://doi.org/10.1007/s11055-021-01096-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-021-01096-0

Keywords

Navigation