Available online 8 April 2024

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Sleep is a physiological process that preserves the integrity of the neuro-immune-endocrine network to maintain homeostasis. Sleep regulates the production and secretion of hormones, neurotransmitters, cytokines and other inflammatory mediators, both at the central nervous system (CNS) and at the periphery. Sleep promotes the removal of potentially toxic metabolites out of the brain through specialized systems such as the glymphatic system, as well as the expression of specific transporters in the blood-brain barrier. The blood-brain barrier maintains CNS homeostasis by selectively transporting metabolic substrates and nutrients into the brain, by regulating the efflux of metabolic waste products, and maintaining bidirectional communication between the periphery and the CNS. All those processes are disrupted during sleep loss. Brain endothelial cells express the blood-brain barrier phenotype, which arises after cell-to-cell interactions with mural cells, like pericytes, and after the release of soluble factors by astroglial endfeet. Astroglia, pericytes and brain endothelial cells respond differently to sleep loss; evidence has shown that sleep loss induces a chronic low-grade inflammatory state at the CNS, which is associated with blood-brain barrier dysfunction. In animal models, blood-brain barrier dysfunction is characterized by increased blood-brain barrier permeability, decreased tight junction protein expression and pericyte detachment from the capillary wall. Blood-brain barrier dysfunction may promote defects in brain clearance of potentially neurotoxic metabolites and byproducts of neural physiology, which may eventually contribute to neurodegenerative diseases. This chapter aims to describe the cellular and molecular mechanisms by which sleep loss modifies the function of the blood-brain barrier.

Section snippetsSleep

Sleep is a rhythmic physiological process characterized by decreased locomotor activity and alertness (Huang et al., 2011, Potter et al., 2016). The World Health Organization Technical Meeting on Sleep and Health concluded that “sleep is a basic human need and is essential for good health, good quality of life and performing well during the day” (World Health Organization, 2004). Various physiological phenomena are carried out during sleep, including immunological and metabolic processes, as

Sleep regulates the neurovascular unit and blood-brain barrier function

The brain has an extensive network of blood vessels to ensure the adequate supply of oxygen and glucose (Friedland and Iadecola, 1991, Roy and Sherrington, 1890); it requires approximately 20% of the total oxygen metabolism (Hyder et al., 2013). If a certain brain region increases its neuronal activity, it demands more nutrients by releasing signaling molecules that lead to local vasodilation ensuing increase in local blood flow, volume, and oxygenation (Meigel et al., 2019). This increase in

Sleep and the glymphatic system

The glymphatic system clears metabolites and toxic byproducts generated by the activity of resident brain cells. The glymphatic system is formed by the astroglial perivascular endfeet, which allow the flux of CSF diffusing along the perivascular space into the brain parenchyma. CSF is thought to enter the brain parenchyma through AQP4 at the endfeet of astrocytes surrounding the periarterial compartment, thereafter, displacing interstitial fluid, waste and debris, and effluxing through the AQP4

Conclusion

Sleep is a complex physiological process in which humans invest approximately a third of their lives. However, the duration, quantity and quality of sleep varies according to age and sex. The sleep-wake cycle regulates the release of hormones, neurotransmitters and cytokines that maintain the optimal function of the organs and systems that allow the well-being. Therefore, the molecular communication between the CNS and the periphery is tightly regulated at the BBB interface. Studies in rodents

Funding

This work was supported by the Universidad Autónoma Metropolitana grant 14407031 to BGG.

References (109)C. IadecolaThe neurovascular unit coming of age: A journey through neurovascular coupling in health and disease

Neuron

(2017)

M.R. Irwin et al.Sleep loss activates cellular inflammatory signaling

Biological Psychiatry

(2008)

J.M. Krueger et al.Sleep function: Toward elucidating an enigma

Sleep Medicine Reviews

(2016)

H.L. McConnell et al.Astrocyte dysfunction and neurovascular impairment in neurological disorders: Correlation or causation?

Neurochemistry International

(2019)

F. Medina-Flores et al.Sleep loss disrupts pericyte-brain endothelial cell interactions impairing blood-brain barrier function

Brain, Behavior, and Immunity

(2020)

H.K. Meier-Ewert et al.Effect of sleep loss on C-Reactive protein, an inflammatory marker of cardiovascular risk

Journal of the American College of Cardiology

(2004)

A.D. Mueller et al.Inhibition of hippocampal neurogenesis by sleep deprivation is independent of circadian disruption and melatonin suppression

Neuroscience

(2011)

A.C. Reynolds et al.Total sleep deprivation, chronic sleep restriction and sleep disruption

(2010)

R.L. Rungta et al.Vascular compartmentalization of functional hyperemia from the synapse to the pia

Neuron

(2018)

W.T. Shearer et al.Soluble TNF-α receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

Journal of Allergy and Clinical Immunology

(2001)

P. Taishi et al.Cytokine mRNA induction by interleukin-1beta or tumor necrosis factor alpha in vitro and in vivo

Brain Research

(2008)

E. Tobaldini et al.Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases

Neuroscience and Biobehavioral Reviews

(2017)

M. Viola-Saltzman et al.Traumatic brain injury and sleep disorders

Neurologic Clinics

(2012)

A.-C. Voirin et al.Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-α) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model

Brain Research

(2020)

J.W. Williams et al.Cytokine circuits in cardiovascular disease

Immunity

(2019)

N.J. Abbott et al.Astrocyte-endothelial interactions at the blood-brain barrier

Nature Reviews. Neuroscience

(2006)

H. Almutairi et al.Classification of sleep stages from EEG, EOG and EMG signals by SSNet (arXiv:2307.05373)

arXiv

(2023)

J.I. Alvarez et al.The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence

Science (New York, N. Y.)

(2011)

D. Attwell et al.Glial and neuronal control of brain blood flow

Nature

(2010)

D. Attwell et al.What is a pericyte?

Journal of Cerebral Blood Flow & Metabolism

(2016)

M. Bellesi et al.Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex

The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

(2017)

H. Benveniste et al.Glymphatic system function in relation to anesthesia and sleep states

Anesthesia and Analgesia

(2019)

A.M. Berger et al.Sleep/wake disturbances in people with cancer and their caregivers: State of the science

Oncology Nursing Forum

(2005)

M.H. BonnetSleep deprivationH. Boutin et al.Role of IL-1α and IL-1β in ischemic brain damage

The Journal of Neuroscience

(2001)

D. Brisevac et al.Extracellular ATP selectively upregulates ecto-nucleoside triphosphate diphosphohydrolase 2 and ecto-5′-nucleotidase by rat cortical astrocytes in vitro

Journal of Molecular Neuroscience

(2015)

C. Cai et al.Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses

Proceedings of the National Academy of Sciences

(2018)

Z. Chen et al.Nuclear factor-κB-like activity increases in murine cerebral cortex after sleep deprivation

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

(1999)

C. Cordon-Cardo et al.Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites

Proceedings of the National Academy of Sciences of the United States of America

(1989)

J. Cui et al.Mechanisms and pathways of innate immune activation and regulation in health and cancer

Human Vaccines & Immunotherapeutics

(2014)

W. Dement et al.The relation of eye movements during sleep to dream activity: An objective method for the study of dreaming

Journal of Experimental Psychology

(1957)

B. Díaz-Castro et al.Astrocyte endfeet in brain function and pathology: Open questions

Annual Review of Neuroscience

(2023)

D.-J. Dijk et al.Sleep physiology, circadian rhythms, waking performance and the development of sleep-wake therapeutics

Handbook of Experimental Pharmacology

(2019)

C.A. DinarelloOverview of the IL‐1 family in innate inflammation and acquired immunity

Immunological Reviews

(2018)

C. Florian et al.Astrocyte-derived adenosine and A1 receptor activity contribute to sleep loss-induced deficits in hippocampal synaptic plasticity and memory in mice

Journal of Neuroscience

(2011)

J. Franco-Pérez et al.Sleep deprivation and sleep recovery modifies connexin36 and connexin43 protein levels in rat brain

Neuroreport

(2012)

R.P. Friedland et al.Roy and Sherrington (1890): A centennial reexamination of On the regulation of the blood-supply of the brain

Neurology

(1991)

V. Gelfo et al.Roles of IL-1 in cancer: From tumor progression to resistance to targeted therapies

International Journal of Molecular Sciences

(2020)

B. Gómez-González et al.REM sleep loss and recovery regulates blood-brain barrier function

Current Neurovascular Research

(2013)

I.G. Gould et al.The capillary bed offers the largest hemodynamic resistance to the cortical blood supply

Journal of Cerebral Blood Flow & Metabolism

(2017)

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