title: Obstructive sleep apnea and cognitive impairment: addressing the blood-brain barrier.
abstract: Increasing data support a connection between obstructive sleep apnea (OSA) 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 OSA 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.
authors.affiliation: Department of Medicine, Division of Sleep Medicine, and Center for Sleep and Circadian Neurobiology, University of Pennsylvania, 125 South 31st Street, Suite 2100, Philadelphia, PA 19104, USA. Electronic address: limdiane@mail.med.upenn.edu.
authors.forename: Diane C
authors.initials: DC
authors.lastname: Lim
authors.affiliation: Department of Medicine, Division of Sleep Medicine, and Center for Sleep and Circadian Neurobiology, University of Pennsylvania, 125 South 31st Street, Suite 2100, Philadelphia, PA 19104, USA. Electronic address: pack@mail.med.upenn.edu.
authors.forename: Allan I
authors.initials: AI
authors.lastname: Pack
mesh_terms: D001812:Blood-Brain Barrier / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000503:physiopathology
keywords: Angiogenesis; Blood–brain barrier; Blood–brain barrier transporters; Chronic inflammation; Cognitive impairment; Hif1α; Hif2α; Leak; Microvessel permeability; Obstructive sleep apnea; Oxidative stress; Oxygen sensor; Peroxisome proliferator-activated receptor; Pore
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