Transport of brain-derived neurotrophic factor across the blood–brain barrier
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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BDNF can enter the brain by freely diffusing across the blood brain barrier.
“BDNF can also enter the brain via freely diffusing across the blood brain barrier (Pan et al., 1998; Mousavi and Jasmin, 2006).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Pan et al., 1998
Serum BDNF is reflective of central nervous system levels.
“BDNF crosses the blood-brain barrier with high capacity and is highly stable over time, thus serum BDNF is reflective of central nervous system levels [5], [13], [14].”
From Associations between social relationship measures, serum brain-derived neurotrophic factor, and risk of stroke and dementia (2017) · cites this paper as [13]
Peripheral BDNF is able to cross the blood-brain barrier.
“An important finding is that peripheral BDNF is able to cross the blood-brain barrier [196]”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [196]
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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
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 37
- Issue
- 12
- Pages
- 1553-1561
- ISSN
- 0028-3908 (ISSN-L)
- 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
- 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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