CHARGE-RELATED ALTERATIONS OF THE CEREBRAL ENDOTHELIUM

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 49  (6) , 662-671
Abstract
In a short-term rat brain perfusion model, the luminal surface of cerebral endothelium was exposed to the following solutions: the polycation protamine sulfate (PS) in a dose of 50, 100 and 500 .mu.g/ml for 1 or 2 min; PS in a dose of 100 .mu.g/ml (or 500 .mu.g/ml) for 1 or 2 min followed by the polyanion heparin in an equivalent dose of 12 U/ml (or 60 U/ml) for 1 or 2 min; heparin alone for 1 or 2 min and Krebs-Ringer-bicarbonate solution as control for 1, 2 or 4 min. The following were studied in the cerebral endothelium: structural alterations by EM, permeability changes to horseradish peroxidase (HRP) by light and EM and charge alterations of luminal surface visualized with colloidal Fe at pH 1.8 by EM. PS resulted in extravasation of HRP throughout the perfused hemispheres in a time- and dose-dependent fashion. In this experimental group, colloidal Fe binding decreased on the luminal surface of the cerebral blood vessels. Heparin perfusion following PS reversed the colloidal Fe staining but failed to prevent the blood barrier opening to HRP. Heparin perfused alone also induced extravasation of HRP in the treated brain hemispheres. In Krebs-Ringer-bicarbonate-perfused control brains extravasation of HRP was encountered only in occasional vascular segments. In all brain hemispheres showing tracer extravasation, EM revealed HRP reaction product in compartments of endothelial tight junctions suggesting opening of interendothelial routes as the structural basis of blood-brain barrier opening. Endothelial cell death reflected by swelling and influx of HRP into endothelial cytoplasm in PS- and/or heparin-perfused hemispheres was probably an additional mechanism explaining tracer extravasation into the neuropil. The results indicate a correlation between the effect of polycation PS and a decrease in the anionic sites of cerebral endothelium. The relationship between charge alteration and barrier opening in this short-term perfusion model is not clear.