Functional effectiveness of the blood-brain barrier to small water-soluble molecules in developing and adult opossum (Monodelphis domestica)
We have evaluated a small water‐soluble molecule, biotin ethylenediamine (BED, 286 Da), as a permeability tracer across the blood‐brain barrier. This molecule was found to have suitable characteristics in that it is stable in plasma, has low plasma protein binding, and appears to behave in a similar...
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Published in | Journal of comparative neurology (1911) Vol. 496; no. 1; pp. 13 - 26 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.05.2006
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Subjects | |
Online Access | Get full text |
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Summary: | We have evaluated a small water‐soluble molecule, biotin ethylenediamine (BED, 286 Da), as a permeability tracer across the blood‐brain barrier. This molecule was found to have suitable characteristics in that it is stable in plasma, has low plasma protein binding, and appears to behave in a similar manner across brain barriers as established by permeability markers such as sucrose. BED, together with a 3000‐Da biotin‐dextran (BDA3000), was used to investigate the effectiveness of tight junctions in cortical vessels during development and adulthood of a marsupial opossum (Monodelphis domestica). Marsupial species are born at an early stage of brain development when cortical vessels are just beginning to appear. The tracers were administered systemically to opossums at various ages and localized in brains with light and electron microscopy. In adults, the tight junctions restricted the movement of both tracers. In neonates, as soon as vessels grow into the neocortex, their tight junctions are functionally restrictive, a finding supported by the presence of claudin‐5 in endothelial cells. However, both tracers are also found within brain extracellular space soon after intraperitoneal administration. The main route of entry for the tracers into immature neocortex appears to be via the cerebrospinal fluid over the outer (subarachnoid) and inner (ventricular) surfaces of the brain. These experiments demonstrate that the previously described higher permeability of barriers to small molecules in the developing brain does not seem to be due to leakiness of cerebral endothelial tight junctions, but to a route of entry probably via the choroid plexuses and cerebrospinal fluid. J. Comp. Neurol. 496:13–26, 2006. © 2006 Wiley‐Liss, Inc. |
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Bibliography: | ArticleID:CNE20885 Melbourne University Early Career Grant ark:/67375/WNG-QDT38FF4-N National Institutes of Health - No. 5RO1 NS043949 istex:39E2FC60F6D8175261C1E5625B8C391E47C5FDAC ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Associate Editor for review Dr Oswald Stewart, University of California-Irvine |
ISSN: | 0021-9967 1096-9861 |
DOI: | 10.1002/cne.20885 |