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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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“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]
In the citing paper
“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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“Due to their ability to cross the blood–brain barrier (BBB) [175, 176], EVs have been considered as potent drug delivery agents in CNS disorders.”
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“Because EVs, particularly those of endosomal origin, are capable of crossing the blood–brain barrier, they carry molecular signatures derived from brain tissue into the systemic circulation [11].”
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“Exosomes secreted from the central nervous system (CNS) act as signaling pathways between nerves, some of which cross the cerebral blood barrier and circulate in the peripheral blood (Matsumoto et al. 2017).”
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“[56] These differences could re fl ect species-speci fi c microRNA pro fi les, especially in brain tissue and in certain environmental situations or disease models, and consequently warrant further investigation.”
Moon, S.-H., Huh, Y. E., & Choi, H. J. (2026) · Future Pharmacology · doi:10.3390/futurepharmacol6010008
“In this context, cell therapy has attracted attention, not only for its secretome and immunomodulatory functions [28–30] but also because extracellular vesicles (EVs) released by cells can cross the BBB to some extent or modulate its function indirectly [31–33].”
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“93 After MSC-EVs have arrived at their target cells, they can communicate with each other via receptor-ligand interactions or be endocytosed to deliver their contents.”
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Chemical design of diagnostic and therapeutic nanoplatforms for cerebrovascular diseases
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Self-citationExtracellular Vesicles in COVID-19: Mechanistic insights and emerging therapeutic strategies.
Mateus, L. C. O., Corrêa, J. R., & de Almeida, P. D. (2025) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202520241216
“In this context, in addition to their roles as therapeutic tools and drug delivery vehicles, EVs can be explored as biomarkers for disease monitoring and treatment (Matsumoto et al. 2018, Garcia-Beltran et al. 2022).”
Metadata
- 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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