Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke
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As part of the neurovascular unit, the blood-brain barrier (BBB) is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and the central nervous system. Disruption of the BBB plays an important role in the development of neurological dysfunction in ischemic stroke. Blood-borne substances and cells have restricted access to the brain due to the presence of tight junctions between the endothelial cells of the BBB. Following stroke, there is loss of BBB tight junction integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality. Thus, understanding principal mediators and molecular mechanisms involved in BBB disruption is critical for the development of novel therapeutics to treat ischemic stroke. This review discusses the current knowledge of how neuroinflammation contributes to BBB damage in ischemic stroke. Specifically, we provide an updated overview of the role of cytokines, chemokines, oxidative and nitrosative stress, adhesion molecules, matrix metalloproteinases, and vascular endothelial growth factor as well as the role of different cell types in the regulation of BBB permeability in ischemic stroke.
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MMP-9 increases blood-brain barrier permeability and promotes BBB breakdown through proteolytic activity.
“Another pro-inflammatory target of GLP-1RAs is matrix metalloproteinase-9 (MMP-9), an enzyme that increases BBB permeability and promotes BBB breakdown through proteolytic activity [77].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [77]
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Xiong, B., Wang, Y., Chen, Y., Xing, S., Liao, Q., Chen, Y., Li, Q., Li, W., & Sun, H. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00910 · Cited by 232 · see citing works
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Blood brain barrier inflammation and potential therapeutic role of phytochemicals
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- Authors
- Yang, C., Hawkins, K. E., Doré, S., & Candelario-Jalil, E.
- Affiliations
- University of Florida (US)
- Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2019-02-01
- Volume
- 316
- Issue
- 2
- Pages
- C135-C153
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- PMC
- PMC6397344
- OpenAlex
- W2899197889
- Cited by
- 871
- References
- 256
- Citations by year
- 2026: 92 · 2025: 167 · 2024: 148 · 2023: 140 · 2022: 138 · 2021: 108 · 2020: 59 · 2019: 19
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NS065849, NS103094, NS095166)
- HHS | NIH | National Center for Complementary and Alternative Medicine (AT007429)
- McKnight Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- blood-brain barrier disruption, ischemic stroke, neuroinflammation, tight junctions, blood-brain barrier permeability, vasogenic edema, hemorrhagic transformation, cytokines, chemokines, oxidative stress, nitrosative stress, adhesion molecules, matrix metalloproteinases, vascular endothelial growth factor, endothelial cells, neurovascular unit
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Brain Ischemia, Humans, Permeability, Oxidative Stress, Inflammation Mediators, Tight Junctions, Stroke, Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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