Macromolecular permeability across the blood-nerve and blood-brain barriers

Joseph F. Poduslo, Geoffry L. Curran, Carole T. Berg

Research output: Contribution to journalArticle

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Abstract

The permeability of insulin (Ins), nerve growth factor (NGF), albumin (Alb), transferrin (Trf), and IgG across the blood-nerve barrier (BNB) and blood-brain barrier (BBB) in normal adult rats was quantified by measuring the (permeability coefficient x surface area) product (PS) with the i.v. bolus-injection technique in the cannulated brachial vein and artery using radioiodinated proteins. The PS values of the BNB for IgG and Alb were low: 0.079 ± 0.029 x 10-6 and 0.101 ± 0.088 x 10-6 ml · g-1 · s-1, (x̄ ± SD, respectively). The PS values for NGF and Trf were 16.1-fold and 25.5-fold higher than for Alb. The PS for Ins across the BNB was 33.190 ± 2.053 x 10-6 ml · g-1 · s-1-a remarkable 329-fold increase compared with Alb. The PS values of the BBB for IgG and Alb in different brain regions were all low, from 0.028 ± 0.017 to 0.151 ± 0.035 x 10-6 ml · g-1 · s-1 (x̄ ± SD). NGF and Trf had comparable PS values from 13- to 32-fold higher than for Alb, except for the brain stem, where the PS for Trf was 66- fold higher than for Alb. The mean PS for Ins across the BBB ranged from 15.78 ± 5.45 x 10-6 ml · g-1 · s-1 for the cortex to 22.62 ± 7.50 x 10-6 ml · g-1 · s-1 for the brain stem-again a remarkable 105- to 390-fold increase relative to Alb. Because reliable PS measurements were obtained for all proteins tested, the BBB and BNB cannot be considered impermeable to proteins-a concept that has plagued brain- and nerve-barrier research. The low PS values for IgG and Alb indicate low rates of transfer; however, Alb, in particular, is the major protein of endoneurial and ventricular fluid, which suggests that these PS values may be significant. Ins had the highest PS values, which likely reflect the mechanism of transport across the barriers-that is, receptor-mediated transport. Because NGF and Trf had PS values 13- to 66-fold higher than for Alb, whether this reflects receptor-mediated uptake, adsorptive-mediated transcytosis, or some other mechanism is unclear. That the PS values for NGF and Trf differ from Alb and IgG clearly suggests, however, a different uptake mechanism. Finally, the remarkably high PS values for Ins across the BBB and BNB identify this protein and its putative receptor on capillary endothelial cells as a potential target for drug delivery into the central and peripheral nervous systems.

Original languageEnglish (US)
Pages (from-to)5705-5709
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number12
DOIs
StatePublished - Jun 7 1994

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Blood-Brain Barrier
Albumins
Permeability
Blood-Nerve Barrier
Transferrin
Nerve Growth Factor
Immunoglobulin G
Insulin
Proteins
Brain Stem
Transcytosis
Brachial Artery
Peripheral Nervous System
Brain
Veins
Central Nervous System
Endothelial Cells
Injections

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Macromolecular permeability across the blood-nerve and blood-brain barriers. / Poduslo, Joseph F.; Curran, Geoffry L.; Berg, Carole T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 12, 07.06.1994, p. 5705-5709.

Research output: Contribution to journalArticle

Poduslo, Joseph F. ; Curran, Geoffry L. ; Berg, Carole T. / Macromolecular permeability across the blood-nerve and blood-brain barriers. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 12. pp. 5705-5709.
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