title: A size selective vascular barrier in the rat area postrema formed by perivascular macrophages and the extracellular matrix.
abstract: The fenestrated microvasculature of the area postrema shows a less restrictive blood-brain barrier than is found in other areas of the CNS. We have studied the expression and relationship of vascular endothelial tight junctional proteins, astrocytes, macrophages, and the extracellular matrix with the extravasation of fluorescently tagged dextrans and sodium fluorescein in the rat area postrema. Glial fibrillary acidic protein (GFAP) -positive astrocytes were present within the area postrema which was surrounded by a dense zone of highly GFAP-reactive astrocytes. Expression of the tight junction proteins claudin-5, -12 and occludin was absent, although diffuse cytoplasmic claudin-1 immunoreactivity was present. The extracellular matrix of the endothelium showed two non-fused thickened layers of laminin immunoreactivity. CD163 and CD169 immunoreactive perivascular macrophages were located within lacunae between these two laminin layers. Fluorescently tagged dextrans (10-70 kDa) passed from the vasculature but were retained between the inner and outer laminin walls and rapidly sequestered by the perivascular CD163 and CD169 macrophages. Three-kilodalton dextran diffused into the parenchyma, but was retained within the boundary of the area postrema at the interface with the highly reactive GFAP-astrocytes, while sodium fluorescein (0.3 kDa) passed from the area postrema into surrounding CNS areas. Our observations suggest that despite the absence of a tight blood-brain barrier, a size selective barrier restricting the movement of blood solutes into the parenchyma is present in the area postrema. We suggest that the rapid uptake by CD163 and CD169 macrophages together with the non-fused laminin immunoreactive layers of the extracellular matrix plays a size selective role in restricting movement of serum proteins and other blood borne macromolecules over 10 kDa in to the area postrema.
authors.affiliation: Medical Research Council Applied Neuroscience Group, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham NG7 2UH, UK. cwills@email.arizona.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Willis
authors.forename: C J
authors.initials: CJ
authors.lastname: Garwood
authors.forename: D E
authors.initials: DE
authors.lastname: Ray
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D031608:Area Postrema / Q000378:metabolism* / Q000648:ultrastructure; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D003911:Dextrans / Q000378:metabolism / Q000493:pharmacokinetics; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008833:Microcirculation / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001798:Blood Proteins; D000098902:CD163 Antigen; D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D063267:Sialic Acid Binding Ig-like Lectin 1