Sleep loss disrupts pericyte-brain endothelial cell interactions impairing blood-brain barrier function

Medina-Flores, Fernanda; Hurtado‐Alvarado, Gabriela; de, Arturo Contis-Montes; López-Cervantes, Stefanie Paola; Königsberg, Mina; Deli, Mária A.; Gómez-González, Beatriz

doi:10.1016/j.bbi.2020.05.077

Cited by 44 publications

(41 citation statements)

References 49 publications

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“…We found that there was a decrease in tight junction protein expression, particularly ZO-1 and occludin, during EA stimulation, but the expression of claudin-5 has not changed significantly. Similarly, there has one study about sleep loss impairing BBB function shown that the changes of occludin and claudin-5 in BBB leakage were inconsistent ( Medina-Flores et al, 2020 ). This could because claudins are important in establishing the tight junction pore pathway, and recent findings have shown that ZO-1 and occludin are important in the leak pathway ( Shen et al, 2011 ).…”

Section: Discussionmentioning

confidence: 98%

Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes

et al. 2020

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The blood-brain barrier (BBB) plays an important role in both the physiological state and pharmacological state of the brain. Transiently enhancing the permeability of the BBB may allow the use of more types of medications for neuropsychiatric diseases. Our previous research revealed that electroacupuncture (EA) stimulation at certain parameters can enhance the permeability of the BBB in Sprague-Dawley rats, but this phenomenon is not well characterized. We propose that specific frequency EA can transiently open the BBB and may be related to the change of tight junctions (TJ). To find the best EA frequency among commonly used frequencies, preliminarily explore the mechanism, we detected BBB permeability by measuring the intensity of Evans Blue and 20 kDa FITC-dextran fluorescence in the cerebral cortex. Then, we used a laser spectrometer, immunofluorescence, western blotting, and transmission electron microscopy to detect the mechanism of BBB opening. Finally, measured brain water content, AQP4, GFAP, Iba1, and used the DeadEnd TM Fluorometric TUNEL System to clear whether the stimulation caused obvious negative effects. The results show that EA stimulation at 2/100 Hz maximally increased BBB permeability, and the BBB closed within 12 h after EA stimulation was removed. EA stimulation increased blood perfusion, c-fos levels, and Substance P expression in the cerebral cortex, decreased ZO-1 and occludin levels and induced ultrastructural changes in TJ morphology. EA stimulation at specific parameters did not cause brain edema, activation of glial cells, or cell apoptosis. This study shows that EA stimulation induces a reversible, frequency-dependent alteration of BBB permeability and proposes a hypothetical mechanism of BBB opening related to vasodilation and TJ disruption. Transiently enhancing the permeability of the BBB with EA at specific parameters may be a new strategies for delivering therapeutics to the central nervous system. Further study of this technology is needed.

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Section: Discussionmentioning

confidence: 98%

Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes

et al. 2020

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“…Sleep and its disorders are known to influence the BBB. Sleep loss impairs the function of the BBB by disrupting the interactions of pericytes and brain endothelial cells (54). Sleep participates in the neural biological regulation by facilitating the elimination of metabolites along the BBB (55).…”

Section: Discussionmentioning

confidence: 99%

Sleep Deprivation Induces Cognitive Impairment by Increasing Blood-Brain Barrier Permeability via CD44

Sun

Hua

et al. 2020

Front. Neurol.

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Sleep deprivation occurs frequently in older adults, which can result in delirium and cognitive impairment. CD44 is a key molecular in blood-brain barrier (BBB) regulation. However, whether CD44 participates in the role of sleep deprivation in cognitive impairment remains unclear. In this study, the effect of sleep deprivation on cognitive ability, tissue inflammation, BBB permeability, and astrocyte activity were evaluated in vivo. The differentially expressed genes (DEGs) were identified by RNA sequencing. A CD44 overexpression in the BBB model was performed in vitro to assess the effect and mechanisms of CD44. Sleep deprivation impaired the learning and memory ability and increased the levels of inflammatory cytokines, along with increased BBB permeability and activated astrocytes in hippocampus tissue. RNA sequencing of the hippocampus tissue revealed that 329 genes were upregulated in sleep deprivation-induced mice compared to control mice, and 147 genes were downregulated. GO and pathways showed that DEGs were mainly involved in BBB permeability and astrocyte activation, including nervous system development, neuron development, and brain development, and neuroactive ligand-receptor interaction. Moreover, the PCR analysis revealed that CD44 was dramatically increased in mice with sleep deprivation induction. The overexpression of CD44 in astrocytes promoted BBB permeability in vitro and induced the expression of the downstream gene NANOG. Our results indicate that sleep deprivation upregulated CD44 expression in hippocampus tissue, and increased BBB permeability, resulting in cognitive impairment.

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“…However, there is emerging evidence that the major complication of sleep loss is neuroinflammation, which induces BBB disruption (Table 1). Indeed, sleep loss per se, including sleep deprivation, sleep restriction, sleep fragmentation, or sleep apnea in human and rodents induces a systemic low-grade inflammation characterized by the release of several molecules, such as cytokines, chemokines, and acute-phase proteins; all of them can promote changes in cellular components of the BBB, particularly on brain endothelial cells [35][36][37][38][39][40][41][42][43][44][45][46]. In this session, we discuss the role of inflammatory mediators that increase during sleep loss and how these changes may alter the BBB permeability as well as we analyze hypothetical mechanisms by which sleep deprivation may induce the BBB disruption, emphasizing the regulatory effect of inflammatory molecules on tight junction proteins.…”

Section: Sleep Loss-associated Neuroinflammation and The Blood-brain Barrier Disruptionmentioning

confidence: 99%

Brain Mechanisms of COVID-19-Sleep Disorders

Semyachkina-Glushkovskaya

Mamedova

Vinnik

et al. 2021

IJMS

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2020 and 2021 have been unprecedented years due to the rapid spread of the modified severe acute respiratory syndrome coronavirus around the world. The coronavirus disease 2019 (COVID-19) causes atypical infiltrated pneumonia with many neurological symptoms, and major sleep changes. The exposure of people to stress, such as social confinement and changes in daily routines, is accompanied by various sleep disturbances, known as ‘coronasomnia’ phenomenon. Sleep disorders induce neuroinflammation, which promotes the blood–brain barrier (BBB) disruption and entry of antigens and inflammatory factors into the brain. Here, we review findings and trends in sleep research in 2020–2021, demonstrating how COVID-19 and sleep disorders can induce BBB leakage via neuroinflammation, which might contribute to the ‘coronasomnia’ phenomenon. The new studies suggest that the control of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for the prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of BBB leakage, and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

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Sleep loss disrupts pericyte-brain endothelial cell interactions impairing blood-brain barrier function

Cited by 44 publications

References 49 publications

Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes

Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes

Sleep Deprivation Induces Cognitive Impairment by Increasing Blood-Brain Barrier Permeability via CD44

Brain Mechanisms of COVID-19-Sleep Disorders

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