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Titolo:
Permeability and route of entry for lipid-insoluble molecules across brainbarriers in developing Monodelphis domestica
Autore:
Ek, CJ; Habgood, MD; Dziegielewska, KM; Potter, A; Saunders, NR;
Indirizzi:
Univ Tasmania, Dept Anat & Physiol, Hobart, Tas 7001, Australia Univ Tasmania Hobart Tas Australia 7001 siol, Hobart, Tas 7001, Australia Univ Tasmania, Dept Pathol, Hobart, Tas 7001, Australia Univ Tasmania Hobart Tas Australia 7001 thol, Hobart, Tas 7001, Australia
Titolo Testata:
JOURNAL OF PHYSIOLOGY-LONDON
fascicolo: 3, volume: 536, anno: 2001,
pagine: 841 - 853
SICI:
0022-3751(20011101)536:3<841:PAROEF>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT CHOROID-PLEXUS; FETAL SHEEP; PEROXIDASE UPTAKE; IMMATURE BRAIN; EPITHELIUM; DIFFUSION; ALBUMIN; OPOSSUM; SYSTEM; GROWTH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Saunders, NR Univ Tasmania, Dept Anat & Physiol, GPO Box 252-24, Hobart, Tas 7001, Australia Univ Tasmania GPO Box 252-24 Hobart Tas Australia 7001 tralia
Citazione:
C.J. Ek et al., "Permeability and route of entry for lipid-insoluble molecules across brainbarriers in developing Monodelphis domestica", J PHYSL LON, 536(3), 2001, pp. 841-853

Abstract

1. We have studied the permeability of blood-brain barriers to small molecules such as [C-14]sucrose, [H-3]inulin, [C-14]L-glucose and [H-3]glycerol from early stages of development (postnatal day 6, P6) in South American opossums (Monodelphis domestica), using a litter-based method for estimating steady-state cerebrospinal fluid (CSF)/plasma and brain/plasma ratios of markers that were injected i.p.2. Steady-state ratios for L-glucose, sucrose and inulin all showed progressive decreases during development. The rate of uptake of L-glucose into the brain and CSF, in short time course experiments (7-24 min) when age-related differences in CSF production can be considered negligible also decreased during development. These results indicate that there is a significant decrease in the permeability of brain barriers to small lipid-insoluble molecules during brain development.3. The steady-state blood/CSF ratio for 3000 Da lysine-fixable biotin-dextran following I.P. injection was shown to be consistent with diffusion fromblood to CSF. It was therefore used to visualise the route of penetration for small lipid-insoluble molecules across brain barriers at P0-30, The proportion of biotin-dextran-positive cells in the choroid plexuses declined in parallel with the age-related decline in permeability to the small-molecular-weight markers; the paracellular (tight junction) pathway for biotin-dextran appeared to be blocked, but biotin-dextran was easily detectable in the CSF. A transcellular route from blood to CSF was suggested by the finding that some choroid plexus epithelial cells contained biotin-dextran.4. Biotin-dextran was also taken up by cerebral endothelial cells in the youngest brains Studied (PO), but in contrast to the CSF, could not be detected in the brain extracellular space (i.e. a significant blood-brain barrier to small-sized lipid-insoluble compounds was already present). However, in immature brains (P0-13) biotin-dextran was taken up by some cells in the brain. These cells generally had contact with the CSF, suggesting that it is likely to have been the 2source of their biotin-dextran. Since the quantitative permeability data suggest that biotin-dextran behaves similarly to the radiolabelled markers used in this study, it is suggested that these markers in the more immature brains were also present intracellularly. Thus, brain/plasma ratios may be a misleading indicator of blood-brain barrier permeability in very immature animals.5. The immunocytochemical staining for biotin-dextran in the CSF, in contrast to the lack of staining in the brain extracellular space, together withthe quantitative permeability data showing that the radiolabelled markers penetrated more rapidly and to a much higher steady-state level in CSF thanin the brain, suggests that lipid-insoluble molecules such as sucrose and inulin reach the immature brain predominantly via the CSF rather than directly across the very few blood vessels that are present at that time.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 02:53:06