Cited by 263Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsTraumatic Brain Injury and Neurovascular Disturbances

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Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

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Michinaga, Shotaro, Koyama, Yutaka·2019·International Journal of Molecular Sciences

DOI 10.3390/ijms20030571PMC PMC6387062

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Abstract

The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.

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Authors: Michinaga, S., & Koyama, Y.
Affiliations: Osaka Ohtani University (JP)
Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyama-Kita Higashinada, Kobe 668-8558, Japan
ORCID: Michinaga, Shotaro
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2019-01-29
Volume: 20
Issue: 3
Pages: 571
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms20030571
PMC: PMC6387062
OpenAlex: W2912925231
Cited by: 263
References: 192
Citations by year: 2026: 30 · 2025: 21 · 2024: 38 · 2023: 44 · 2022: 43 · 2021: 48 · 2020: 28 · 2019: 11
FWCI: 3.38
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Japan Society for the Promotion of Science (16K18890, 18K06695)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: blood-brain barrier, astrocytes, blood-brain barrier permeability, brain damage, traumatic brain injury, cerebral ischemia, vascular endothelial growth factor, matrix metalloproteinases, nitric oxide, endothelin-1, glutamate, angiopoietin-1, Sonic hedgehog, glial cell line-derived neurotrophic factor, retinoic acid, insulin-like growth factor I, apolipoprotein E, cerebral edema, neuroinflammation
MeSH terms: Animals, Astrocytes, Blood-Brain Barrier, Brain Injuries, Humans, Tight Junctions

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Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

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