Cited by 1,354Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNerve injury and regeneration

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Transport of brain-derived neurotrophic factor across the blood–brain barrier

Pan, Weihong, Banks, William A, Fasold, Melita B, Bluth, Jonathan, Kastin, Abba J·1998·Neuropharmacology

DOI 10.1016/s0028-3908(98)00141-5

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Abstract

Brain-derived neurotrophic factor (BDNF) is a potential therapeutic agent for degenerative disorders of the central nervous system. In this report, we investigated the ability of BDNF to cross the blood-brain barrier (BBB). BDNF was stable in blood up to 60 min after i.v. injection, with evidence for aggregation, and had an early, rapid influx into brain. By 10 min, most of the BDNF sequestered by the cerebral cortex was associated with the parenchyma rather than with the endothelial cells, demonstrating complete passage across the BBB. A small dose of unlabeled BDNF enhanced the entry of 125I-BDNF from blood to brain after an i.v. bolus injection, whereas larger doses had no effect. In contrast, a large dose of unlabeled BDNF inhibited the influx of 125I-BDNF during in situ brain perfusion. After intracerebroventricular injection, the efflux of BDNF from brain to blood occurred at a rate similar to that for reabsorption of cerebrospinal fluid, and no evidence for self-inhibition was found. Therefore, we conclude that intact BDNF in the peripheral circulation crosses the BBB by a high-capacity, saturable transport system.

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Authors: Pan, W., Banks, W. A., Fasold, M. B., Bluth, J., & Kastin, A. J.
Affiliations: Tulane University (US)
St. Louis VA Medical Center (US)
Corresponding author: Pan, Weihong
ORCID: Pan, Weihong
Banks, William A
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 1998-12
Volume: 37
Issue: 12
Pages: 1553-1561
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/s0028-3908(98)00141-5
OpenAlex: W1972280500
Cited by: 1,354
References: 25
Citations by year: 2026: 33 · 2025: 53 · 2024: 85 · 2023: 64 · 2022: 63 · 2021: 100 · 2020: 89 · 2019: 77 · 2018: 66 · 2017: 76 · 2016: 82 · 2015: 65 · 2014: 78 · 2013: 62 · 2012: 53
FWCI: 3.94
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords: brain-derived neurotrophic factor, blood-brain barrier, saturable transport, cerebral cortex, cerebrospinal fluid reabsorption, neurotrophic therapy
MeSH terms: Animals, Blood-Brain Barrier, Brain, Capillaries, Cerebrovascular Circulation, Humans, Injections, Intravenous, Iodine Radioisotopes, Kinetics, Male, Mice, Inbred ICR, Recombinant Proteins, Regression Analysis, Technetium Tc 99m Aggregated Albumin, Time Factors, Brain-Derived Neurotrophic Factor, Mice

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Transport of brain-derived neurotrophic factor across the blood–brain barrier

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