Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: electron microscopist’s view

• Published in: Brain Research Reviews Vol. 42; no. 3; pp. 221 - 242
• Main Authors: Vorbrodt, Andrzej W., Dobrogowska, Danuta H.
• Format: Book Review Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.06.2003; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier - physiology; Blood–brain barrier; Blood–CSF barrier; Brain - cytology; Brain - metabolism; Brain - ultrastructure; Cells, Cultured; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Electron microscopy; Endothelial cell; Endothelium - physiology; Endothelium - ultrastructure; Epithelial Cells - physiology; Epithelial Cells - ultrastructure; Fundamental and applied biological sciences. Psychology; Humans; Immunogold cytochemistry; Intercellular junction; Intercellular Junctions - metabolism; Intercellular Junctions - ultrastructure; Microscopy, Immunoelectron - methods; Vertebrates: nervous system and sense organs; Endothelial cell; Blood–CSF barrier; Immunogold cytochemistry; JAM, junctional adhesion molecule; Cellular and molecular biology; BBB, blood–brain barrier; Electron microscopy; ZO, zonula occludens protein; Blood–brain barrier; EC, endothelial cell; EM, electron microscopy; AJs, adherens junctions; TJs, tight junctions; CSF, cerebrospinal fluid; Intercellular junction; Central nervous system; Cell cell interaction; Review; Cerebrospinal fluid; Blood brain barrier; Blood-CSF barrier; Blood-brain barrier; Ultrastructure; Brain (vertebrata)
• ISSN: 0165-0173; 1872-6321
• DOI: 10.1016/S0165-0173(03)00177-2

In this review, we have tried to summarize the current knowledge on the distribution of important molecular components of intercellular junctions—both tight junctions (TJs) and adherens junctions (AJs)—at the level of ultrastructure. For this purpose, immunogold procedure was applied to ultrathin sections of brain samples obtained from mice, rats, and humans and embedded in hydrophilic resin Lowicryl K4M. The results of our observations performed with transmission electron microscopy (EM) are discussed and compared with findings of other authors. Although the main structures responsible for the barrier and fence functions of the blood–brain barrier (BBB) and blood–CSF barrier are TJs present between endothelial cells (ECs) of brain capillaries and epithelial cells of the choroid plexus, their functional characteristics (e.g. tightness of the barrier evaluated by electrical resistance) differ significantly. Therefore, our main attention is focused on the presence and distribution of both intrinsic, i.e. integral membrane (transmembrane), molecules such as occludin, claudins, and junctional adhesion molecule (JAM) in TJs, and cadherins in AJs, as well as peripheral molecules of both types of junctions, e.g. zonula occludens (ZO) proteins and catenins. The latter group of molecules connects transmembrane proteins with the cell cytoskeleton. A close spatial association of the TJ proteins with those of AJs indicates that both junctional types are intermingled in the BBB type of endothelium. One of most important purposes of this work is to find out the junction-associated molecules that can serve as sensitive markers of normal or disturbed function of brain barriers. Understanding the structural–functional relations between molecular components of junctional complexes in physiological and experimental conditions of both barriers can provide important information about the etiology of various pathological conditions of the central nervous system and also help to elaborate new therapeutic approaches.