Ontogeny of the blood-brain barrier

Saunders, Norman

doi:10.1016/s0014-4835(77)80046-8

Cited by 118 publications

(62 citation statements)

References 53 publications

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“…While the formation is nearly complete in most brain areas at birth, the brain barriers remain functionally immature and permeable, and in some species, it remains in such a state long after birth. 42,43 An age-dependent maturation also occurs in the BCB. 44 During early development, the leaky structure of brain barriers is physiologically necessary to accommodate the high demand of blood-borne nutrients by the growing brain.…”

Section: Discussionmentioning

confidence: 99%

Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro

Shi¹,

Zheng

2007

Hum Exp Toxicol

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The cell type constructing the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) is entirely different, ie, endothelia in BBB and epithelia in BCB. Nonetheless, both barriers share a common character - the tight junctions (TJ) between adjacent cells. This study investigated the consequence of lead (Pb) exposure on the tightness of BCB. In an in vitro BCB transwell model, using immortalized choroidal epithelial Z310 cells, we found that early exposure to Pb (prior to the formation of tight barrier) at 5 and 10 μM, significantly reduced the tightness of BCB, as evidenced by a 20% reduction in transepithelial electrical resistance (TEER) values ( P <0.05), and >20% increase in the paracellular permeability of [14C]sucrose ( P <0.05). Exposure to Pb after the formation of tight barrier, however, did not cause any detectable barrier dysfunction. RT-PCR and Western blot analyses on typical TJ proteins revealed that Pb exposure decreased both the mRNA and protein levels of claudin-1, with the membrane-bound claudin-1 more profoundly affected than cytosolic claudin-1. Pb exposure, however, had no significant effect on ZO1 and occludin. These data suggest that Pb exposure selectively alters the cellular level of claudin-1, which, in turn, reduces the tightness and augments the permeability of tight blood-CSF barrier. The immature barrier appears to be more vulnerable to Pb toxicity than the mature, well-developed, brain barrier, the fact possibly contributing to Pb-induced neurotoxicity among young children.

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Section: Discussionmentioning

confidence: 99%

Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro

Shi¹,

Zheng

2007

Hum Exp Toxicol

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“…Many investigators have noted that the BBB of immature animals is more permeable than that of adults (see Saunders, 1977 for review). The basis for this increased permeability is not presently known.…”

Section: Discussionmentioning

confidence: 99%

“…Although the reason for this enhanced permeability is unknown, possible mechanisms include leaky tight junctions, increased pinocytosis or transendothelial channels. The reader is referred to Saunders (1977) for a review of this subject since it was not investigated in our study.…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in metabolism and transport properties of capillaries isolated from rat brain.

Betz¹,

Goldstein²

1981

The Journal of Physiology

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SUMMARY1. Capillaries were isolated from the brains oft-to 45-day-old rats in order to study the development of metabolic and transport aspects of the blood-brain barrier.2. The hydroxyproline content of capillary hydrolysates increased nearly threefold between 5 and 45 days of age. This finding is consistent with histological studies showing thickening of capillary basement membrane during development.3. The activities of L-DOPA decarboxylase and monoamine oxidase were greatest in capillaries from 10-day-old rat brain. Thus, the metabolic blood-brain barrier for amine precursors is present during early development.4. Capillaries from all ages were able to metabolize glucose, fi-hydroxybutyrate and palmitate. The rate of glucose oxidation more than doubled between 21 and 30 days of age but subsequently decreased. In contrast, f-hydroxybutyrate and palmitate oxidation increased throughout development. These data suggest a sparing effect by alternate fuels on glucose metabolism.5. Capillary glucose uptake was similar at 10 and 30 days of age and activity of the ouabain-sensitive K+ pump (measured using 86Rb+) was relatively constant at all ages. In contrast, Na+-dependent neutral amino acid transport was not present until after 21 days of age. Since this transport system may be responsible for the active efflux of neutral amino acids from brain to blood, it is likely that this process does not occur at the immature blood-brain barrier.6. We conclude that various aspects of brain capillary functions show distinct developmental patterns which may be related to changes in blood-brain barrier permeability during development.

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“…While its formation is nearly complete in most brain areas at birth, the barrier remains functionally immature and permeable, and in some species, it remains in such a state long after birth (69,70). An age-dependent maturation also occurs in the BCB (1).…”

Section: Age and Brain Barriersmentioning

confidence: 99%

Neurotoxicology of the Brain Barrier System: New Implications

Zheng

2001

Journal of Toxicology: Clinical Toxicology

105

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The concept of a barrier system in the brain has existed for nearly a century. The barrier that separates the blood from the cerebral interstitial fluid is defined as the blood-brain barrier, while the one that discontinues the circulation between the blood and cerebrospinal fluid is named the blood-cerebrospinal fluid barrier. Evidence in the past decades suggests that brain barriers are subject to toxic insults from neurotoxic chemicals circulating in blood. The aging process and some disease states render barriers more vulnerable to insults arising inside and outside the barriers. The implication of brain barriers in certain neurodegenerative diseases is compelling, although the contribution of chemical-induced barrier dysfunction in the etiology of any of these disorders remains poorly understood. This review examines what is currently understood about brain barrier systems in central nervous system disorders by focusing on chemical-induced neurotoxicities including those associated with nitrobenzenes, N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic acid. Contemporary research questions arising from this growing understanding show enormous promises for brain researchers, toxicologists, and clinicians.

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Ontogeny of the blood-brain barrier

Cited by 118 publications

References 53 publications

Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro

Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro

Developmental changes in metabolism and transport properties of capillaries isolated from rat brain.

Neurotoxicology of the Brain Barrier System: New Implications

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