scholarly journals Obstructive Sleep Apnea, Hypercoagulability, and the Blood–Brain Barrier

2021 ◽  
Vol 10 (14) ◽  
pp. 3099
Author(s):  
Cindy Zolotoff ◽  
Laurent Bertoletti ◽  
David Gozal ◽  
Valentine Mismetti ◽  
Pascale Flandrin ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Blood Brain Barrier ◽  
Platelet Activation ◽  
Coagulation Factor ◽  
Brain Barrier ◽  
Factor Activity ◽  
Blood Brain ◽  
Obstructive Sleep ◽  
Neural Dysfunction

Obstructive sleep apnea (OSA) is characterized by repeated episodes of intermittent hypoxia (IH) and is recognized as an independent risk factor for vascular diseases that are mediated by a multitude of mechanistic pathophysiological cascades including procoagulant factors. The pro-coagulant state contributes to the development of blood clots and to the increase in the permeability of the blood–brain barrier (BBB). Such alteration of BBB may alter brain function and increase the risk of neurodegenerative diseases. We aim to provide a narrative review of the relationship between the hypercoagulable state, observed in OSA and characterized by increased coagulation factor activity, as well as platelet activation, and the underlying neural dysfunction, as related to disruption of the BBB. We aim to provide a critical overview of the existing evidence about the effect of OSA on the coagulation balance (characterized by increased coagulation factor activity and platelet activation) as on the BBB. Then, we will present the emerging data on the effect of BBB disruption on the risk of underlying neural dysfunction. Finally, we will discuss the potential of OSA therapy on the coagulation balance and the improvement of BBB.

Blood-brain barrier dysfunction in aging induces hyperactivation of TGFβ signaling and chronic yet reversible neural dysfunction

2019 ◽  
Vol 11 (521) ◽  
pp. eaaw8283 ◽  
Author(s):  
Vladimir V. Senatorov ◽  
Aaron R. Friedman ◽  
Dan Z. Milikovsky ◽  
Jonathan Ofer ◽  
Rotem Saar-Ashkenazy ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Transforming Growth Factor ◽  
Neurovascular Unit ◽  
Brain Barrier ◽  
Aging Brain ◽  
Tgfβ Signaling ◽  
Blood Brain ◽  
Tgfβ Receptors ◽  
Neural Dysfunction

Aging involves a decline in neural function that contributes to cognitive impairment and disease. However, the mechanisms underlying the transition from a young-and-healthy to aged-and-dysfunctional brain are not well understood. Here, we report breakdown of the vascular blood-brain barrier (BBB) in aging humans and rodents, which begins as early as middle age and progresses to the end of the life span. Gain-of-function and loss-of-function manipulations show that this BBB dysfunction triggers hyperactivation of transforming growth factor–β (TGFβ) signaling in astrocytes, which is necessary and sufficient to cause neural dysfunction and age-related pathology in rodents. Specifically, infusion of the serum protein albumin into the young rodent brain (mimicking BBB leakiness) induced astrocytic TGFβ signaling and an aged brain phenotype including aberrant electrocorticographic activity, vulnerability to seizures, and cognitive impairment. Furthermore, conditional genetic knockdown of astrocytic TGFβ receptors or pharmacological inhibition of TGFβ signaling reversed these symptomatic outcomes in aged mice. Last, we found that this same signaling pathway is activated in aging human subjects with BBB dysfunction. Our study identifies dysfunction in the neurovascular unit as one of the earliest triggers of neurological aging and demonstrates that the aging brain may retain considerable latent capacity, which can be revitalized by therapeutic inhibition of TGFβ signaling.

Obstructive Sleep Apnea and Platelet Activation

CHEST Journal ◽  
2004 ◽  
Vol 126 (2) ◽  
pp. 339-341 ◽  
Author(s):  
Lyle J. Olson ◽  
Eric J. Olson ◽  
Virend K. Somers
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Platelet Activation ◽  
Obstructive Sleep

Exosomes, blood–brain barrier, and cognitive dysfunction in pediatric sleep apnea

2017 ◽  
Vol 15 (4) ◽  
pp. 261-267 ◽  
Author(s):  
Leila Kheirandish-Gozal ◽  
Abdelnaby Khalyfa ◽  
David Gozal
Keyword(s):  
Sleep Apnea ◽  
Cognitive Dysfunction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Pediatric Sleep

scholarly journals Plasma Extracellular Vesicles in Children with OSA Disrupt Blood–Brain Barrier Integrity and Endothelial Cell Wound Healing In Vitro

2019 ◽  
Vol 20 (24) ◽  
pp. 6233 ◽  
Author(s):  
Abdelnaby Khalyfa ◽  
David Gozal ◽  
Leila Kheirandish-Gozal
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Cognitive Deficits ◽  
Brain Barrier ◽  
Neurocognitive Deficits ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Obstructive Sleep

Pediatric obstructive sleep apnea (P-OSA) is associated with neurocognitive deficits and endothelial dysfunction, suggesting the possibility that disruption of the blood–brain barrier (BBB) may underlie these morbidities. Extracellular vesicles (EVs), which include exosomes, are small particles involved in cell–cell communications via different mechanisms and could play a role in OSA-associated end-organ injury. To examine the roles of EVs in BBB dysfunction, we recruited three groups of children: (a) absence of OSA or cognitive deficits (CL, n = 6), (b) OSA but no evidence of cognitive deficits (OSA-NC(−), n = 12), and (c) OSA with evidence of neurocognitive deficits (OSA-NC(+), n = 12). All children were age-, gender-, ethnicity-, and BMI-z-score-matched, and those with OSA were also apnea–hypopnea index (AHI)-matched. Plasma EVs were characterized, quantified, and applied on multiple endothelial cell types (HCAEC, HIAEC, human HMVEC-D, HMVEC-C, HMVEC-L, and hCMEC/D3) while measuring monolayer barrier integrity and wound-healing responses. EVs from OSA children induced significant declines in hCMEC/D3 transendothelial impedance compared to CL (p < 0.001), and such changes were greater in NC(+) compared to NC(−) (p < 0.01). The effects of EVs from each group on wound healing for HCAEC, HIAEC, HMVED-d, and hCMEC/D3 cells were similar, but exhibited significant differences across the three groups, with evidence of disrupted wound healing in P-OSA. However, wound healing in HMVEC-C was only affected by NC(+) (p < 0.01 vs. NC(−) or controls (CO). Furthermore, no significant differences emerged in HMVEC-L cell wound healing across all three groups. We conclude that circulating plasma EVs in P-OSA disrupt the integrity of the BBB and exert adverse effects on endothelial wound healing, particularly among OSA-NC(+) children, while also exhibiting endothelial cell type selectivity. Thus, circulating EVs cargo may play important roles in the emergence of end-organ morbidity in pediatric OSA.

Platelet activation, epinephrine, and blood pressure in obstructive sleep apnea syndrome

Neurology ◽  
1998 ◽  
Vol 51 (1) ◽  
pp. 188-195 ◽  
Author(s):  
I. Eisensehr ◽  
B. L. Ehrenberg ◽  
S. Noachtar ◽  
K. Korbett ◽  
A. Byrne ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Platelet Activation ◽  
Sleep Apnea Syndrome ◽  
Obstructive Sleep ◽  
Apnea Syndrome
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