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Review
. 2017 Jan;37(1):4-24.
doi: 10.1177/0271678X16679420. Epub 2016 Nov 11.

Age-associated physiological and pathological changes at the blood-brain barrier: A review

Franciska Erdő  1 , László Denes  2 , Elizabeth de Lange  3
Affiliations
Review

Age-associated physiological and pathological changes at the blood-brain barrier: A review

Franciska Erdő et al. J Cereb Blood Flow Metab. 2017 Jan.

Abstract

The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication.

Keywords: Aging; blood–brain barrier; endothelial cells; neurodegenerative disorders; transport systems.

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Figures

Figure 1.
Figure 1.
The most important cellular elements of blood–brain barrier (modified from http://www.hcvpi.bham.ac.uk/staff/NF.html).
Figure 2.
Figure 2.
Causes, characteristics and consequences of BBB breakdown (modified from Obermeier et al.).
Figure 3.
Figure 3.
Localization of membrane transporters in the endothelial cells, at the BBB in rodents (modified from the website of Solvo Biotechnology).
Figure 4.
Figure 4.
Tight and adherens junctions components. Tight junctions (TJs) are the most apical intercellular junctions in ECs. Their major transmembrane components are the claudins, occludin and adhesion molecules (JAMs), whereas their cytoplasmic components are zonula occludens (ZOs) proteins. Adherens junctions (AJs) are localized just below TJs; their transmembrane components are cadherins and nectins that complex respectively the cytoplasmic components β-catenin and afadin.
Figure 5.
Figure 5.
The role of blood–brain barrier transport in brain homeostasis of amyloid-β. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders.
Figure 6.
Figure 6.
Possible mechanisms leading to BBB disruption in MS. For explanation, please see the main text (modified from Minagar and Alexander).
See this image and copyright information in PMC

References

    1. Rascher G, Wolburg H. The blood-brain barrier in the aging brain. In: Vellis JSd. (ed). Neuroglia in the aging brain, Totowa, NJ: Humana Press Inc., 2002, pp. 305–320. .
    1. Clarke E, O'Malley CD. The human brain and spinal cord. A historical study illustrated by writings from antiquity to the twentieth century, Berkeley: University of California Press, 1968.
    1. Alavijeh MS, Chishty M, Qaiser MZ, et al. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx 2005; 2: 554–571. - PMC - PubMed
    1. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 2004; 16: 1–13. - PubMed
    1. Abbott NJ. Dynamics of CNS barriers: evolution, differentiation, and modulation. Cell Mol Neurobiol 2005; 25: 5–23. - PMC - PubMed

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