Abstract
The blood–brain barrier is a dynamic structure, collectively referred to as the neurovascular unit. It is responsible for the exchange of blood, oxygen, ions, and other molecules between the peripheral circulation and the brain compartment. It is the main entrance to the central nervous system and as such critical for the maintenance of its homeostasis. Dysfunction of the blood–brain barrier is a characteristic of several neurovascular pathologies. Moreover, physiological changes, environmental factors, nutritional habits, and psychological stress can modulate the tightness of the barrier. In this contribution, we summarize our current understanding of structure and function of this important component of the brain. We also describe the neurological deficits associated with its damage. A special emphasis is placed in the effect of the exposure to xenobiotics and pollutants in the permeability of the barrier. Finally, current protective strategies as well as the culture models to study this fascinating structure are discussed.
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modified from Rustenhoven et al. (2017)
modified from Nian et al. (2020)
modified from Stone et al. (2019)
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Abbreviations
- BBB :
-
Blood–brain barrier
- BECs :
-
Endothelial cells
- CNS :
-
Central nervous system
- NVU :
-
Neurovascular unit
- TJs :
-
Tight junctions
- AD :
-
Alzheimer disease
- PD :
-
Parkinson disease
- JAMs :
-
Junction adhesion molecules
- ZO :
-
Zonula occluddens
- TEER :
-
Transendothelial electrical resistance
- JACOP :
-
Junction-associated coiled-coil protein
- MAGI:
-
Membrane-associated guanylate kinase
- AJs :
-
Adherens junctions
- PECAM :
-
Platelet endothelial cell adhesion molecules
- MRP :
-
Multidrug-resistance associated protein
- TGFβ :
-
Transforming growth factor-β
- GDNF :
-
Glial-derived neurotrophic factor
- bFGF :
-
Basic fibroblast growth factor
- AQP4 :
-
Water channel aquaporin 4
- IL-1β :
-
Interleukin-1β
- TNF-α :
-
Tumor necrosis factor-α
- ABC :
-
ATP-binding cassette transporters
- GLUT1 :
-
Glucose transporter 1
- MFSD2A :
-
Major facilitator superfamily domain containing 2A
- NKCC :
-
Na+-K+-Cl− cotransporter
- Pgp :
-
P-glycoprotein
- Bcrp :
-
Breast cancer resistance protein
- LRP1 :
-
Lipoprotein receptor-related protein 1
- SLCs :
-
Solute carriers
- PDGFR :
-
Platelet-derived growth factor
- VEGF :
-
Vascular endothelial growth factor
- Aβ :
-
Amyloid beta
- RAGE :
-
Receptor for advanced glycation end-products
- MMPs :
-
Matrix metalloproteinases
- HIF-1 α:
-
Hypoxia-inducible factor-1α
- DHA :
-
Acid docosahexaenoic
- HPA :
-
Hypothalamic pituitary adrenal
- S100β :
-
S100 calcium binding protein B
- METH :
-
Methamphetamine
- APC :
-
Activated protein C
- TBI :
-
Traumatic brain injury
- ALS :
-
Ameotrophic lateral sclerosis
- PAR1 :
-
Protease activated receptor 1
- PI3K :
-
Phosphatidylinositol-4,5-bisphosphate 3-kinase
- HBMECs :
-
Human brain endothelial cells
- ISF :
-
Insterstitial fluid
- IL-6:
-
Interleukin-6
- NAc:
-
Nucleus accumbens
- HADC1:
-
Histone deacetylase 1
- APOE4:
-
Apolipoprotein-E4
- MS:
-
Multiple sclerosis
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Acknowledgements
Fredy Sanchez Cano is supported by Conacyt and the work in the lab is supported by grants from Conacyt (255087) to AO.
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Conacyt 255087, Conacyt PhD scholarship 755526.
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AO conceived the original idea and wrote the final version. FSC and LCRHK prepared the first draft of the manuscript and the figures. All authors have read and approved the final manuscript.
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Sanchez-Cano, F., Hernández-Kelly, L.C. & Ortega, A. The Blood–Brain Barrier: Much More Than a Selective Access to the Brain. Neurotox Res 39, 2154–2174 (2021). https://doi.org/10.1007/s12640-021-00431-0
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DOI: https://doi.org/10.1007/s12640-021-00431-0