Blood–brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
Abstract
The blood-brain barrier (BBB) is the specialized system of brain microvascular endothelial cells (BMVEC) that shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream. The close interaction between BMVEC and other components of the neurovascular unit (astrocytes, pericytes, neurons, and basement membrane) ensures proper function of the central nervous system (CNS). Transport across the BBB is strictly limited through both physical (tight junctions) and metabolic barriers (enzymes, diverse transport systems). A functional polarity exists between the luminal and abluminal membrane surfaces of the BMVEC. As a result of restricted permeability, the BBB is a limiting factor for the delivery of therapeutic agents into the CNS. BBB breakdown or alterations in transport systems play an important role in the pathogenesis of many CNS diseases (HIV-1 encephalitis, Alzheimer's disease, ischemia, tumors, multiple sclerosis, and Parkinson's disease). Proinflammatory substances and specific disease-associated proteins often mediate such BBB dysfunction. Despite seemingly diverse underlying causes of BBB dysfunction, common intracellular pathways emerge for the regulation of the BBB structural and functional integrity. Better understanding of tight junction regulation and factors affecting transport systems will allow the development of therapeutics to improve the BBB function in health and disease.
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Claudins and occludins are major tight junction proteins; claudins display essential barrier function and occludins ensure tightness of tight junctions.
“Claudins and occludins that situate in two-cell contacts are the major tight junction proteins.95,96 Claudins display essential barrier function and occludins ensure the tightness of the tight junctions.97”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [97]
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“…into the brain [72], it cannot be excluded that several physio-pathological states, such as ageing, infections, cancer, diabetes, atherosclerosis, stroke, and post-traumatic and environmental pollutant-associated injuries [200–205], could allow PCSK9 loading into the brain by destabilizing the BBB.”
- Authors
- Persidsky, Y., Ramirez, S. H., Haorah, J., & Kanmogne, G. D.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Persidsky, Yuri
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2006-07-06
- Volume
- 1
- Issue
- 3
- Pages
- 223-236
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- OpenAlex
- W1996574563
- Cited by
- 922
- References
- 13
- Citations by year
- 2026: 28 · 2025: 49 · 2024: 64 · 2023: 51 · 2022: 58 · 2021: 52 · 2020: 65 · 2019: 45 · 2018: 43 · 2017: 43 · 2016: 52 · 2015: 47 · 2014: 54 · 2013: 55 · 2012: 54
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R37AA015913, R01AA015913)
- National Institute of Mental Health (R01MH065151, R01-MH65151)
- National Institute of Neurological Disorders and Stroke (P01NS043985)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- blood-brain barrier, brain microvascular endothelial cells, neurovascular unit, tight junctions, blood-brain barrier permeability, BBB dysfunction, central nervous system disorders, tight junction regulation, pro-inflammatory mediators, HIV-1 encephalitis, Alzheimer's disease, multiple sclerosis, Parkinson's disease, ischemia, brain tumors
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Brain Diseases, Chemotaxis, Leukocyte, Humans, Cell Adhesion Molecules, Tight Junctions, Endothelial Cells
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