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The blood-brain barrier in brain homeostasis and neurological diseases
Open accessAbstract
Brain endothelial cells are unique among endothelial cells in that they express apical junctional complexes, including tight junctions, which quite resemble epithelial tight junctions both structurally and functionally. They form the blood-brain-barrier (BBB) which strictly controls the exchanges between the blood and the brain compartments by limiting passive diffusion of blood-borne solutes while actively transporting nutrients to the brain. Accumulating experimental and clinical evidence indicate that BBB dysfunctions are associated with a number of serious CNS diseases with important social impacts, such as multiple sclerosis, stroke, brain tumors, epilepsy or Alzheimer's disease. This review will focus on the implication of brain endothelial tight junctions in BBB architecture and physiology, will discuss the consequences of BBB dysfunction in these CNS diseases and will present some therapeutic strategies for drug delivery to the brain across the BBB.
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“Integrity of the BBB can be compromised because of exposures to certain toxicants, such as pesticides, mixed vehicle emissions, and tobacco smoke, as well as certain health conditions including diabetes and neurological disorders reviewed in Neurotoxicity of PFAS in Sensitive Populations, through molecular alterations in barrier function (Gupta et al., 1999; Weiss et al., 2009; Mazzone et al., 201”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Weiss et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“PFAS exposure could be more hazardous for individuals with pre-existing neurological conditions or a predisposition for these diseases”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Weiss et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Many neurological conditions, including Alzheimer’s disease (AD), Parkinson’s Disease (PD), multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), Huntington’s disease, and brain tumors, confer heightened damage by PFAS and other toxicants by functionally compromising the BBB”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Weiss et al., 2009
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In the citing paper
“The experiment demonstrated the remarkably high capability of the tested phytocompounds in crossing the BBB, with asiaticoside showing the highest permeability, followed by madecassoside. Notably, the compounds also showed higher permeability coefficient values than donepezil, a drug commonly used for AD. 43”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [43]
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“In the same study using primary porcine brain endothelial cells, asiaticoside and madecassoside were proved to be efficient in crossing the BBB at a high rate without exerting any toxic effects, and while preserving the BBB tight junction integrity, making them desirable neurotherapeutics.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [43]
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“In the aforementioned study by Hanapi et al., 43 madecassoside, in particular, was observed to protect PBECs against H2O2‐induced oxidative stress.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [43]
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Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Pathobiology of ischaemic stroke: an integrated view
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01401-0 · Cited by 3,943
A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis
Polman, C. H., O'Connor, P. W., Havrdová, E., Hutchinson, M., Kappos, L., Miller, D. H., Phillips, J. T., LUBLIN, F. D., Giovannoni, G., Wajgt, A., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa044397 · Cited by 3,433
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Noseworthy, J. H., Lucchinetti, C. F., Rodriguez, M., & Weinshenker, B. G. (2000) · New England Journal of Medicine · doi:10.1056/nejm200009283431307 · Cited by 3,016
The blood-brain barrier/neurovascular unit in health and disease
Hawkins, B. T., & Davis, T. P. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.2.4 · Cited by 2,661
Multifunctional strands in tight junctions
Tsukita, S., Furuse, M., & Itoh, M. (2001) · Nature reviews. Molecular cell biology · doi:10.1038/35067088 · Cited by 2,578
Plate, K. H., Breier, G., Weich, H. A., & Risau, W. (1992) · Nature · doi:10.1038/359845a0 · Cited by 2,262
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Winkler, E. A., Bell, R. D., & Zlokovic, B. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2946 · Cited by 962
The blood-brain barrier: Physiology and strategies for drug delivery
Pandit, R., Chen, L., & Götz, J. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.11.009 · Cited by 651
Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease
Pistollato, F., Sumalla Cano, S., Elio, I., Masias Vergara, M., Giampieri, F., & Battino, M. (2016) · Nutrition Reviews · doi:10.1093/nutrit/nuw023 · Cited by 496
Sankowski, R., Mader, S., & Valdés-Ferrer, S. I. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00028 · Cited by 351
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349
Metadata
- Authors
- Weiss, N., Miller, F., Cazaubon, S., & Couraud, P.-O.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Couraud, Pierre-Olivier
- ORCID
- Weiss, Nicolas
- Venue
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 1788
- Issue
- 4
- Pages
- 842-857
- ISSN
- 0005-2736 (ISSN-L)
- OpenAlex
- W1992883702
- Cited by
- 731
- References
- 244
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 37 · 2023: 36 · 2022: 62 · 2021: 61 · 2020: 54 · 2019: 42 · 2018: 48 · 2017: 58 · 2016: 56 · 2015: 31 · 2014: 41 · 2013: 45 · 2012: 40
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- 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 endothelial cells, tight junctions, apical junctional complex, BBB dysfunction, brain homeostasis, multiple sclerosis, stroke, brain tumors, epilepsy, Alzheimer's disease, central nervous system disorders, brain drug delivery
- MeSH terms
- Blood-Brain Barrier, Brain, Cell Movement, Homeostasis, Humans, Leukocytes, Meningitis, Viral, Multiple Sclerosis, Nervous System Diseases, Permeability, Meningitis, Bacterial, Tight Junctions, Neurodegenerative Diseases, Stroke, Endothelial Cells
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