Contraction of human brain endothelial cells induced by thrombogenic and fibrinolytic factors: An in vitro cell culture model

Zoltan Nagy, K. Kolev, Eva Csonka, Marta Pek, R. Machovich

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Vasogenic brain edema is a frequent complication of ischemic stroke. The mechanism of the blood-brain barrier opening that underlies the edema formation is poorly understood. In the present study we examined the response of endothelial cells cultured from adult human brain to thrombogenic and fibrinolytic factors that possibly accumulate in the occluded vascular segments in ischemic stroke. Methods The changes in the morphology of cultured human brain microvascular endothelial cells were observed by phasecontrast light microscopy and quantified with computerized morphometry. Results Active proteases (eg, thrombin, plasmin, urokinase) as well as heparin and protamine, but not fibrinogen and antithrombin III, produced significant changes in endothelial cell morphology. Two shape patterns of contraction were observed: protamine treatment resulted in rounded cells with a decrease in both cell perimeter and area, whereas all other agents induced spiderlike cell morphology with increased perimeter and reduced area. The rate of contraction was dose dependent, and at comparable enzyme concentrations plasmin produced faster contraction than thrombin. The observed changes were reversed 3 hours after abrogating the treatment. Conclusions In an in vitro model we have demonstrated that factors involved in thrombus formation and dissolution induce endothelial cell contraction, which could affect focally the permeability of the blood-brain barrier by opening paracellular avenues between endothelial cells in vivo. Thus, the genesis of brain edema in thromboembolic stroke or occasionally during fibrinolytic therapy can be attributed in part to the contact of these factors with the microvascular endothelium.

Original languageEnglish
Pages (from-to)265-270
Number of pages6
JournalStroke
Volume26
Issue number2
Publication statusPublished - 1995

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Endothelial Cells
Cell Culture Techniques
Brain
Protamines
Fibrinolysin
Stroke
Brain Edema
Blood-Brain Barrier
Thrombin
Antithrombin III
Thrombolytic Therapy
Urokinase-Type Plasminogen Activator
Fibrinogen
Endothelium
Blood Vessels
Heparin
Microscopy
Permeability
Edema
Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing
  • Neuroscience(all)

Cite this

Contraction of human brain endothelial cells induced by thrombogenic and fibrinolytic factors : An in vitro cell culture model. / Nagy, Zoltan; Kolev, K.; Csonka, Eva; Pek, Marta; Machovich, R.

In: Stroke, Vol. 26, No. 2, 1995, p. 265-270.

Research output: Contribution to journalArticle

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AU - Machovich, R.

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