The Transport Mechanism of Extracellular Vesicles at the Blood-Brain Barrier
Abstract
Recently, extracellular vesicles (EVs), like exosomes and microvesicles, have attracted attention as potent carriers of intercellular communication throughout the body, including the brain. They transmit biological signals from donor cells to recipient cells, and recent evidence suggests that they may even carry such signals to distant destinations through peripheral circulation. In the central nervous system (CNS), EVs contribute to maintaining normal neuronal function, as well as to the pathological development of neurodegenerative diseases. Although some evidence has suggested that EVs can cross the blood-brain barrier (BBB), moving from the peripheral circulation to the CNS, the mechanisms by which EVs facilitate communication between peripheral tissues and the CNS are not well understood. The BBB is a dynamic interface that regulates molecular trafficking between the peripheral circulation and the CNS. However, there is limited mechanistic understanding of how bloodborne EVs cross the BBB under physiological and pathological conditions. In this review, we focus on current knowledge of trafficking of EVs between the peripheral circulation and the brain. Moreover, we describe hypothetical transport routes by which EVs may cross the BBB based on previous reports. Further investigation is needed to understand the precise mechanisms by which EVs are transported across the BBB.
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EVs have inherent targeting capabilities and can cross the BBB, facilitating efficient delivery of therapeutic cargo to the CNS.
“In addition, EVs have inherent targeting capabilities and can cross the BBB, facilitating efficient delivery of therapeutic cargo to the CNS [54–57].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [56]
Brain-derived EVs have the ability to penetrate the BBB and be released into peripheral circulation.
“Brain-derived EVs have been found to harbor the ability to penetrate the BBB. This breakdown is crucial as it potentially allows for releasing these EVs into peripheral circulation [54–57].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [56]
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“However, the mechanisms are still not clear and multiple mechanisms may be involved.(44) MIC and MBC are generally used to evaluate the effects of antibacterial agents.”
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“EVs help in remote cell-to-cell signal transmission and cross the blood–brain barrier (BBB) without damaging the structure [16].”
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Pathophysiology of blood-brain barrier in brain tumor. Novel therapeutic advances using nanomedicine
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Exosome- and extracellular vesicle-based approaches for the treatment of lysosomal storage disorders
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The emerging role of exosomes in communication between the periphery and the central nervous system
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“103 Exosomes originating from leukemia could be of great value, as they can modify the integrity of the connection between endothelial cells in the body and even facilitate the passage into the brain.”
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“Intravenous CDC-EVs have the ability to cross the BBB as shown in topographical distribution studies; we noted the presence of CDC-EVs in the ischemic zone, but not evident elsewhere.”
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“Modifying exosomes with ligands that target these receptors offers a promising approach to further enhance delivery efficiency to the CNS [279].”
Exosomes-Based Nanomedicine for Neurodegenerative Diseases: Current Insights and Future Challenges
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“Because of these, crossing the BBB has gained much attention within the scientific and health communities.”
BackgroundInfluentialMicrobiota-Derived Extracellular Vesicle as Emerging Actors in Host Interactions
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“It has also been hypothesized that [84] the most likely mechanisms of BEV distribution to the CNS are by crossing the BBB [246] and vagal nerve transport [247].”
BackgroundExosomes: current knowledge and future perspectives
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“10 There are two potential stops along the transcytosis pathway.”
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“Further, given the important role of EVs in cell–cell communication [43,44], packaging of GFAP protein in EVs and their circulation via plasma serve multiple purposes [28].”
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Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
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“This transport, however, can be mediated by exosomes, which were reported to carry nucleic acid and proteins across BBB [13].”
Influential
- Authors
- Matsumoto, J., Stewart, T., Banks, W. A., & Zhang, J.
- Affiliations
- University of Washington (US)
- VA Puget Sound Health Care System (US)
- Corresponding author
- Zhang, Jing
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2018-02-15
- Volume
- 23
- Issue
- 40
- Pages
- 6206-6214
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2754129305
- Cited by
- 267
- References
- 0
- Citations by year
- 2026: 18 · 2025: 40 · 2024: 29 · 2023: 22 · 2022: 41 · 2021: 39 · 2020: 39 · 2019: 25 · 2018: 13
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (U01NS082137, U01NS091272)
- National Institute of Environmental Health Sciences (R01ES019277, P30ES007033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- extracellular vesicles, blood-brain barrier, exosomes, microvesicles, intercellular communication, neurodegenerative diseases, blood-brain barrier permeability, central nervous system
- MeSH terms
- Extracellular Vesicles, Animals, Biological Transport, Blood-Brain Barrier, Humans
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