Serum Proteins Bypass the Blood-Brain Fluid Barriers for Extracellular Entry to the Central Nervous System
Identifieur interne : 001C26 ( Istex/Checkpoint ); précédent : 001C25; suivant : 001C27Serum Proteins Bypass the Blood-Brain Fluid Barriers for Extracellular Entry to the Central Nervous System
Auteurs : Richard D. Broadwell [Royaume-Uni] ; Michael V. Sofroniew [Royaume-Uni]Source :
- Experimental Neurology [ 0014-4886 ] ; 1993.
Abstract
Abstract: Extracellular pathways circumventing the mammalian blood-brain fluid barriers (e.g., blood-brain and blood-CSF barriers) have been investigated in the rat by immunohistochemical localization of the endogenous serum proteins albumin, IgG, complement C-9, and IgM and by the exogenous tracer protein horseradish peroxidase (HRP). A demonstrable extracellular pathway into the central nervous system (CNS) is evident at the level of the subarachnoid space/pial surface. Immunoreaction products for the serum proteins and reaction product of intravenously administered HRP are identified over the entire pial surface, in the Virchow-Robin spaces and subpial cortical grey matter, and within phagocytes occupying the subarachnoid space/pial surface and perivascular clefts throughout the CNS. From specific circumventricular organs (e.g., median eminence, area postrema, subfornical organ), well known to lie outside the blood-brain barrier (BBB), each of the blood-borne proteins readily enters adjacent white and grey matter and the ventricular system for subsequent rostrocaudal labeling of the ependymal cell lining. Similar immunohistechemical and blood-borne HRP results are obtained in the CNS of the neonatal rat. Peroxidase delivered into the aorta of postmortem adult rats confirms the presence of a BBB in brain sites containing blood vessels impermeable to blood-borne HRP and the absence of a BBB in sites revealed as leaky to blood-borne HRP in the live rat. The results suggest blood-borne macromolecules, including those of the immune and complement systems, have potential widespread, extracellular distribution within the CNS and cerebrospinal fluid from sites deficient in a BBB (e.g., subarachnoid space/pial surface, circumventricular organs). These observations may have important clinical implications regarding experimental and pathologic autoimmune dysfunction within the CNS and impact on the interpretation of potential transcytosis of blood-borne peptides and proteins through the cerebral endothelium in vivo. A summary diagram of suspected extracellular and intracellular pathways circumventing the blood-brain fluid barriers is provided.
Url:
DOI: 10.1006/exnr.1993.1059
Affiliations:
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Serum Proteins Bypass the Blood-Brain Fluid Barriers for Extracellular Entry to the Central Nervous System</title><author><name sortKey="Broadwell, Richard D" sort="Broadwell, Richard D" uniqKey="Broadwell R" first="Richard D." last="Broadwell">Richard D. Broadwell</name></author><author><name sortKey="Sofroniew, Michael V" sort="Sofroniew, Michael V" uniqKey="Sofroniew M" first="Michael V." last="Sofroniew">Michael V. 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Broadwell</name><affiliation wicri:level="2"><country>Royaume-Uni</country><placeName><region type="country">Angleterre</region></placeName><wicri:cityArea>Division of Neurological Surgery, Department of Surgery, and Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201; and Department of Anatomy, University of Cambridge, Cambridge CB2 3DY</wicri:cityArea></affiliation></author><author><name sortKey="Sofroniew, Michael V" sort="Sofroniew, Michael V" uniqKey="Sofroniew M" first="Michael V." last="Sofroniew">Michael V. Sofroniew</name><affiliation wicri:level="2"><country>Royaume-Uni</country><placeName><region type="country">Angleterre</region></placeName><wicri:cityArea>Division of Neurological Surgery, Department of Surgery, and Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201; and Department of Anatomy, University of Cambridge, Cambridge CB2 3DY</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Experimental Neurology</title><title level="j" type="abbrev">YEXNR</title><idno type="ISSN">0014-4886</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1993">1993</date><biblScope unit="volume">120</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="245">245</biblScope><biblScope unit="page" to="263">263</biblScope></imprint><idno type="ISSN">0014-4886</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0014-4886</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Extracellular pathways circumventing the mammalian blood-brain fluid barriers (e.g., blood-brain and blood-CSF barriers) have been investigated in the rat by immunohistochemical localization of the endogenous serum proteins albumin, IgG, complement C-9, and IgM and by the exogenous tracer protein horseradish peroxidase (HRP). A demonstrable extracellular pathway into the central nervous system (CNS) is evident at the level of the subarachnoid space/pial surface. Immunoreaction products for the serum proteins and reaction product of intravenously administered HRP are identified over the entire pial surface, in the Virchow-Robin spaces and subpial cortical grey matter, and within phagocytes occupying the subarachnoid space/pial surface and perivascular clefts throughout the CNS. From specific circumventricular organs (e.g., median eminence, area postrema, subfornical organ), well known to lie outside the blood-brain barrier (BBB), each of the blood-borne proteins readily enters adjacent white and grey matter and the ventricular system for subsequent rostrocaudal labeling of the ependymal cell lining. Similar immunohistechemical and blood-borne HRP results are obtained in the CNS of the neonatal rat. Peroxidase delivered into the aorta of postmortem adult rats confirms the presence of a BBB in brain sites containing blood vessels impermeable to blood-borne HRP and the absence of a BBB in sites revealed as leaky to blood-borne HRP in the live rat. The results suggest blood-borne macromolecules, including those of the immune and complement systems, have potential widespread, extracellular distribution within the CNS and cerebrospinal fluid from sites deficient in a BBB (e.g., subarachnoid space/pial surface, circumventricular organs). These observations may have important clinical implications regarding experimental and pathologic autoimmune dysfunction within the CNS and impact on the interpretation of potential transcytosis of blood-borne peptides and proteins through the cerebral endothelium in vivo. A summary diagram of suspected extracellular and intracellular pathways circumventing the blood-brain fluid barriers is provided.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li></region></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Broadwell, Richard D" sort="Broadwell, Richard D" uniqKey="Broadwell R" first="Richard D." last="Broadwell">Richard D. Broadwell</name></region><name sortKey="Sofroniew, Michael V" sort="Sofroniew, Michael V" uniqKey="Sofroniew M" first="Michael V." last="Sofroniew">Michael V. Sofroniew</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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