The blood brain barrier: Insights from development and ageing

Delaney, Conor P.; Campbell, Matthew

doi:10.1080/21688370.2017.1373897

Cited by 28 publications

(23 citation statements)

References 101 publications

(109 reference statements)

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“…Healthy aging is associated with a series of morphological, metabolic and epigenetic alterations, limiting regeneration and plasticity, and making cells/tissue vulnerable to diseases, infection and stress. In general, barrier tissues in undergo age-dependent remodeling manifested as changes in functional status including increased permeability (Delaney and Campbell, 2017;Parrish, 2017). Age-related increases in BBB permeability have been widely report in recent years.…”

Section: Discussionmentioning

confidence: 99%

Decline in Sirtuin-1 expression and activity plays a critical role in blood-brain barrier permeability in aging

Stamatovic

Martínez-Revollar

et al. 2019

Neurobiology of Disease

110

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Accumulating evidence suggest that cerebral microvascular disease increases with advancing age and is associated with lacunar stroke, leukoaraiosis, vascular dementia and Alzheimer disease. Increased blood brain barrier (BBB) permeability/leakage takes "center stage" in ongoing age-related vascular/brain parenchymal injury. Although significant effort has been made in defining the gene mutations and risk factors involved in microvascular alterations in vascular dementia and Alzheimer disease, the intra- and intercellular pathogenic mechanisms responsible for vascular hyperpermeability are still largely unknown. The present study aimed to reveal the ongoing senescence process in brain endothelial cells and its effect on BBB integrity in healthy/non-disease conditions. An analysis of BBB integrity during the life span of C56Bl6 mice (young, 2-6 months; middle-aged, 6-12, months; old, 16-22 months) showed increased BBB permeability for different molecular sized tracers (sodium fluorescein, inulin and 20 kDa dextran) in aged mice which was accompanied by modifications in tight junction (TJ) complex organization, manifested as altered TJ protein expression (particularly claudin-5). A gene screening analysis of aging associated markers in brain microvessels isolated from "aged" mice (C56Bl6, 18-20 months) and human brain samples showed a significant decline in sirtuin-1 expression (Sirt1; ~2.8-fold) confirmed at mRNA and protein levels and by activation assay. Experiments in Sirt1 transgenic mice and brain endothelial cell-specific Sirt1 knockout mice indicated that Sirt1 affects BBB integrity, with loss increasing permeability. Similarly, in vitro, overexpressing Sirt1 or increasing Sirt1 activity with an agonist (Sirt1720) protected against senescence-induced brain endothelial barrier hyperpermeability, stabilized claudin-5/ZO-1 interactions and rescued claudin-5 expression. These findings reveal a novel role of Sirt1 in modulating aging-associated BBB persistent leakage.

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Section: Discussionmentioning

confidence: 99%

Decline in Sirtuin-1 expression and activity plays a critical role in blood-brain barrier permeability in aging

Stamatovic

Martínez-Revollar

et al. 2019

Neurobiology of Disease

110

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“…Breakdown of the paracellular pathway, pericyte loss, and transcellular permeability can exacerbate the events linked with age, and can lead to the extravasation of blood-borne material. The susceptibility of endothelium towards many intrinsic destructive agents is known to increase with aging [114]. Again, these facts may provide some explanations of why the SARS-CoV-2 particles were detected in all post-mortem nervous tissue biopsy examined (see Table 1).…”

Section: Blood-nervous System Barriers (Bnsbs)mentioning

confidence: 88%

“…As most neurological disorders in COVID-19 patients are demonstrated in somewhat aged patients, the well-documented effects of age on the endothelial/epithelial barriers and specifically of the BNSB should be kept in mind. The exponential decline of integrity/permeability of these barriers is linked to age as reviewed in detail by Delaney and Campell [114]. It is becoming increasingly evident that the pericytes are susceptible to agedependent deterioration at the BBB.…”

Section: Blood-nervous System Barriers (Bnsbs)mentioning

confidence: 99%

See 1 more Smart Citation

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

Uversky¹,

Elrashdy²,

Aljadawi³

et al. 2020

Preprint

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Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

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“…Gaseous molecules such as oxygen (O 2 ) and carbon dioxide (CO 2 ), as well as small lipophilic molecules less than 500 Da can diffuse freely through brain ECs. Brain ECs are attached to each other by specialized 'tight' junctions (TJs) consisting of various molecular components (Chow and Gu, 2015;Delaney and Campbell, 2017). The TJs form the physical barrier of the BBB (Reese and Karnovsky, 1967) and regulate permeability of the endothelial layer.…”

Section: Effects Of Stroke On Endothelial Cell Structure and Moleculamentioning

confidence: 99%