Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/5335
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Type: Journal article
Title: Electron microscope study of blood-brain barrier opening induced by immunological targeting of the endothelial barrier antigen
Author: Ghabriel, M.
Zhu, C.
Leigh, C.
Citation: Brain Research, 2002; 934(2):140-151
Publisher: Elsevier Science Bv
Issue Date: 2002
ISSN: 0006-8993
1872-6240
Statement of
Responsibility: 
Mounir N. Ghabriel, Chunni Zhu and Chris Leigh
Abstract: Barrier vessels in the central nervous system are lined with endothelial cells which constitute the blood–brain barrier (BBB) and show selective expression of certain biochemical markers. One of these, the endothelial barrier antigen (EBA), is specific to the rat. The exact role of EBA in the BBB is not known, although several studies have shown a correlation between the reduction in EBA expression in endothelial cells and the opening of the BBB. However, in these studies it was not possible to determine if EBA reduction was a primary event or was secondary to opening of the BBB. A recent light microscope study demonstrated that immunological targeting of EBA in vivo, by intravenous injection of a monoclonal antibody (anti-EBA), leads to acute and widespread opening of the BBB. In the current study we have employed this model together with tracer application and immunoperoxidase electron microscopy to determine the site of binding of the injected antibody and the route of opening of the BBB. The results showed that (a) the anti-EBA injected in vivo became bound to brain endothelial cells, principally to luminal membranes. (b) Endothelial cells showed widened intercellular junctions and increased cytoplasmic vesicles and vacuoles. (c) Many perivascular astrocytic processes were swollen. (d) The macromolecular tracer HRP was present in vesicles, vacuoles, widened paracellular clefts, the perivascular space and brain parenchyma. In conclusion, the in vivo targeting of EBA leads to opening of the BBB apparently via paracellular and transcellular routes. This model is useful for the study of vascular permeability in the CNS and experimental manipulation of the BBB. It may have a potential application in experimental studies on drug delivery throughout the CNS.
Keywords: Blood–brain barrier; Endothelial cell; Endothelial barrier antigen; Immunoelectron microscopy; Horseradish peroxidase
Rights: Copyright © 2002 Elsevier Science B.V. All rights reserved.
RMID: 0020020353
DOI: 10.1016/S0006-8993(02)02416-2
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/506048/description#description
Appears in Collections:Anatomical Sciences publications

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