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Obstructive sleep apnea and cognitive impairment: Addressing the blood-brain barrier

Journal

SLEEP MEDICINE REVIEWS
Volume 18, Issue 1, Pages 35-48

Publisher

W B SAUNDERS CO LTD
DOI: 10.1016/j.smrv.2012.12.003

Keywords

Obstructive sleep apnea; Blood-brain barrier; Cognitive impairment; Oxidative stress; Oxygen sensor; Hif1 alpha; Hif2 alpha; Chronic inflammation; Peroxisome proliferator-activated receptor; Angiogenesis; Microvessel permeability; Leak; Blood-brain barrier transporters; Pore

Funding

  1. NIH [T32HL07713, K12 HL090021, HL094307]
  2. Sleep Foundation

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Increasing data support a connection between obstructive sleep apnea (USA) and cognitive impairment but a causal link has yet to be established. Although neuronal loss has been linked to cognitive impairment, emerging theories propose that changes in synaptic plasticity can cause cognitive impairment. Studies demonstrate that disruption to the blood brain barrier (BBB), which is uniquely structured to tightly maintain homeostasis inside the brain, leads to changes in the brain's microenvironment and affects synaptic plasticity. Cyclical intermittent hypoxia is a stressor that could disrupt the BBB via molecular responses already known to occur in either USA patients or animal models of intermittent hypoxia. However, we do not yet know if or how intermittent hypoxia can cause cognitive impairment by. mechanisms operating at the BBB. Therefore, we propose that initially, adaptive homeostatic responses at the BBB occur in response to increased oxygen and nutrient demand, specifically through regulation of influx and efflux BBB transporters that alter microvessel permeability. We further hypothesize that although these responses are initially adaptive, these changes in BBB transporters can have long-term consequences that disrupt the brain's microenvironment and alter synaptic plasticity leading to cognitive impairment. (C) 2013 Elsevier Ltd. All rights reserved.

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