Neurobiology and Neuropathophysiology of Obstructive Sleep Apnea

Significant advancements have been made over the past three decades to better understand the disease entity of obstructive sleep apnea and the mechanisms by which this prevalent disorder imparts injury. Once considered a disorder of reversible sleepiness and insignificant arterial oxygen desaturations because of their intermittency, obstructive sleep apnea is now considered an independent risk factor for cardiovascular morbidity and mortality and an important contributor to neurocognitive impairment and neural injury as well as metabolic dysfunction. The rapidly fluctuating oxygen patterns are now believed to be central to oxidative injury in the brain and peripheral organs. Recent studies in both humans with sleep apnea and animal models of the disorder have increased our understanding of the molecular mechanisms underlying both the disorder and its sequelae, providing great insight into the significance of the disorder and bringing us closer to finding therapies to prevent or reduce both obstructive sleep apnea and it morbidities.

[1]  Rajesh Kumar,et al.  Brain structural changes in obstructive sleep apnea. , 2008, Sleep.

[2]  J. Halberstadt Sleep-disordered breathing. , 1993, The New England journal of medicine.

[3]  Christian Guilleminault,et al.  The association between obstructive sleep apnea and neurocognitive performance--the Apnea Positive Pressure Long-term Efficacy Study (APPLES). , 2011, Sleep.

[4]  G. Aston-Jones,et al.  Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model , 2007, The Journal of Neuroscience.

[5]  Takao Shimizu,et al.  Platelet-activating factor receptor. , 2002, Journal of biochemistry.

[6]  R. Dziewas,et al.  Increased prevalence of obstructive sleep apnoea in patients with Charcot–Marie–Tooth disease: a case control study , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[7]  R. Pedrosa,et al.  The Effects of Continuous Positive Airway Pressure on Prehypertension and Masked Hypertension in Men With Severe Obstructive Sleep Apnea , 2011, Hypertension.

[8]  D. Gozal,et al.  Apolipoprotein E-deficient mice exhibit increased vulnerability to intermittent hypoxia-induced spatial learning deficits. , 2005, Sleep.

[9]  Paul M. Suratt,et al.  FLUOROSCOPIC AND COMPUTED TOMOGRAPHIC FEATURES OF THE PHARYNGEAL AIRWAY IN OBSTRUCTIVE SLEEP APNEA , 1983 .

[10]  S. Takagi,et al.  Effects of incomplete ionization of impurities in poly-Si gate and band gap narrowing on direct tunneling gate leakage current , 2001 .

[11]  T. Gislason,et al.  Sleep‐disordered breathing and glucose metabolism in hypertensive men: a population‐based study , 2001, Journal of internal medicine.

[12]  A. Malhotra,et al.  Pathophysiology & genetics of obstructive sleep apnoea. , 2010, The Indian journal of medical research.

[13]  R. Millman,et al.  One negative polysomnogram does not exclude obstructive sleep apnea. , 1993, Chest.

[14]  Peter Sörös,et al.  Axonal polyneuropathy in obstructive sleep apnoea , 2001, Journal of neurology, neurosurgery, and psychiatry.

[15]  B. Desgranges,et al.  A combined neuropsychological and brain imaging study of obstructive sleep apnea , 2009, Journal of sleep research.

[16]  T. Young,et al.  Effects of sleep-disordered breathing on cerebrovascular regulation: A population-based study. , 2010, American journal of respiratory and critical care medicine.

[17]  J. Montserrat,et al.  Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial , 2010, BMJ : British Medical Journal.

[18]  A. Malhotra,et al.  Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. , 2003 .

[19]  J. Remmers,et al.  Pathogenesis of upper airway occlusion during sleep. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[20]  G. Mora,et al.  Sleep-related breathing disorders in amyotrophic lateral sclerosis. , 2003, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[21]  E. Fletcher,et al.  Renin activity and blood pressure in response to chronic episodic hypoxia. , 1999, Hypertension.

[22]  D. Bliwise,et al.  Factors associated with nightly variability in sleep-disordered breathing in the elderly. , 1991, Chest.

[23]  M. Wolf,et al.  Nocturnal cerebral hemodynamics in snorers and in patients with obstructive sleep apnea: a near-infrared spectroscopy study. , 2010, Sleep.

[24]  E. Phillipson,et al.  Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. , 1997, The Journal of clinical investigation.

[25]  S. Ancoli-Israel,et al.  Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. , 2011, Journal of the American Medical Association (JAMA).

[26]  T. Similowski,et al.  Residual sleepiness in obstructive sleep apnoea: phenotype and related symptoms , 2011, European Respiratory Journal.

[27]  N. Prabhakar,et al.  Intermittent hypoxia augments acute hypoxic sensing via HIF-mediated ROS , 2010, Respiratory Physiology & Neurobiology.

[28]  Demosthenes Bouros,et al.  Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome. , 2009, Sleep.

[29]  Ronald R Grunstein,et al.  Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. , 2008, Proceedings of the American Thoracic Society.

[30]  J. Kirkness,et al.  Effect of end-expiratory lung volume on upper airway collapsibility in sleeping men and women. , 2010, Journal of applied physiology.

[31]  B. Malow,et al.  Obstructive sleep apnea is common in medically refractory epilepsy patients , 2000, Neurology.

[32]  A. Guz,et al.  Reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in awake man. , 1993, Sleep.

[33]  T Douglas Bradley,et al.  Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications. , 2011, Journal of the American College of Cardiology.

[34]  R. Horner Neuromodulation of hypoglossal motoneurons during sleep , 2008, Respiratory Physiology & Neurobiology.

[35]  M. Berthon-Jones,et al.  Influence of moderate alcohol consumption on obstructive sleep apnoea with and without AutoSet nasal CPAP therapy. , 1996, The European respiratory journal.

[36]  F. Perez-Vizcaino,et al.  Carotid body function and ventilatory responses in intermittent hypoxia. evidence for anomalous brainstem integration of arterial chemoreceptor input , 2011, Journal of cellular physiology.

[37]  A. Guz,et al.  The influence of induced hypocapnia and sleep on the endogenous respiratory rhythm in humans. , 1991, The Journal of physiology.

[38]  V. Somers,et al.  Obstructive sleep apnea and cardiovascular disease. , 2009, Circulation journal : official journal of the Japanese Circulation Society.

[39]  J. Dempsey,et al.  A sleep-induced apneic threshold. , 1990, Progress in clinical and biological research.

[40]  E. Ringelstein,et al.  Atherosclerosis and Obstructive Sleep Apnea in Patients with Ischemic Stroke , 2007, Cerebrovascular Diseases.

[41]  J. Prudlo,et al.  Sleep disordered breathing in medically stable patients with myasthenia gravis , 2007, European journal of neurology.

[42]  A. Malhotra,et al.  A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis. , 2011, Sleep.

[43]  C. Hart,et al.  The role of NADPH oxidase in chronic intermittent hypoxia-induced pulmonary hypertension in mice. , 2009, American journal of respiratory cell and molecular biology.

[44]  D. Greenburg,et al.  Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis. , 2009, The American journal of medicine.

[45]  G. Loughlin,et al.  Diagnostic criteria for obstructive sleep apnea syndrome in children , 1992, Pediatric pulmonology.

[46]  Pooja Budhiraja,et al.  Sleep-disordered breathing and cardiovascular disorders. , 2010, Respiratory care.

[47]  T. Bashir,et al.  Sustained sleep fragmentation results in delayed changes in hippocampal-dependent cognitive function associated with reduced dentate gyrus neurogenesis , 2010, Neuroscience.

[48]  Raanan Arens,et al.  Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. , 2003, American journal of respiratory and critical care medicine.

[49]  D. Kripke,et al.  Sleep-disordered breathing in community-dwelling elderly. , 1991, Sleep.

[50]  Alvar Agusti,et al.  Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study , 2005, The Lancet.

[51]  M. Bayley,et al.  Influence of Continuous Positive Airway Pressure on Outcomes of Rehabilitation in Stroke Patients With Obstructive Sleep Apnea , 2011, Stroke.

[52]  Y. Ohno,et al.  Role of gp91phox-containing NADPH oxidase in the deoxycorticosterone acetate-salt-induced hypertension. , 2006, European journal of pharmacology.

[53]  F. Tinahones,et al.  Effect of CPAP on Oxidative Stress and Circulating Progenitor Cell Levels in Sleep Patients With Apnea-Hypopnea Syndrome , 2011, Respiratory Care.

[54]  Remmers Je,et al.  Pathogenesis of upper airway occlusion during sleep , 1978 .

[55]  Daniel J Buysse,et al.  Sleep–Related Breathing Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in Clinical Research , 2000 .

[56]  T. Young,et al.  Excess weight and sleep-disordered breathing. , 2005, Journal of applied physiology.

[57]  E. Ringelstein,et al.  Treatment for obstructive sleep apnoea: effect on peripheral nerve function , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[58]  D. Gozal,et al.  Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat , 2001, The Journal of Neuroscience.

[59]  J. Dempsey,et al.  Mechanisms of the cerebrovascular response to apnoea in humans , 2003, The Journal of physiology.

[60]  W. Smoker,et al.  Hypoglossal Nerve , 1987 .

[61]  J. Stradling,et al.  Mechanisms of vascular damage in obstructive sleep apnea , 2010, Nature Reviews Cardiology.

[62]  K. Alberti,et al.  Diagnostic criteria , 1976, Diabetologia.

[63]  Marie Diener-West,et al.  Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. , 2010, American journal of respiratory and critical care medicine.

[64]  R. Chervin,et al.  Hypoglossal nerve conduction findings in obstructive sleep apnea , 2010, Muscle & nerve.

[65]  H. Hakonarson,et al.  Fatty-acid binding protein 4 gene polymorphisms and plasma levels in children with obstructive sleep apnea. , 2011, Sleep medicine.

[66]  M. Aldrich,et al.  Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. , 1999, Sleep.

[67]  Andrea Falini,et al.  Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. , 2011, American journal of respiratory and critical care medicine.

[68]  N. Naidoo,et al.  Eif-2a Protects Brainstem Motoneurons in a Murine Model of Sleep Apnea , 2008, The Journal of Neuroscience.

[69]  Sonia Ancoli-Israel,et al.  Altered brain activation during response inhibition in obstructive sleep apnea , 2009, Journal of sleep research.

[70]  T. D. Robinson,et al.  Heavy snoring as a cause of carotid artery atherosclerosis. , 2008, Sleep.

[71]  N. Punjabi The epidemiology of adult obstructive sleep apnea. , 2008, Proceedings of the American Thoracic Society.

[72]  V. Somers,et al.  Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea , 2011, Hypertension.

[73]  Hamburger Rj,et al.  Sleep apnea in renal failure. , 1997 .

[74]  E. Klann,et al.  NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. , 2005, American journal of respiratory and critical care medicine.

[75]  P. Nolan,et al.  Selected Contribution: Effects of sleep-wake state on the genioglossus vs. diaphragm muscle responses to CO2 in rats , 2002 .

[76]  Manisha Verma,et al.  Tissue vibration induces carotid artery endothelial dysfunction: a mechanism linking snoring and carotid atherosclerosis? , 2011, Sleep.

[77]  G. Pien,et al.  Update on sleep and its disorders. , 2011, Annual review of medicine.

[78]  B. Wuyam,et al.  Peripheral neuropathy in sleep apnea. A tissue marker of the severity of nocturnal desaturation. , 1999, American journal of respiratory and critical care medicine.

[79]  J. Haze,et al.  Obstructive sleep apnea. , 1987, Cranio : the journal of craniomandibular practice.

[80]  R. Rogers,et al.  Obstructive sleep apnea. , 1996, The New England journal of medicine.

[81]  Maria Grazia Marciani,et al.  Cognitive profile and brain morphological changes in obstructive sleep apnea , 2011, NeuroImage.

[82]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[83]  D. Wacker,et al.  The effects of sleep disruption on the treatment of a feeding disorder. , 2005, Journal of applied behavior analysis.

[84]  A. Malhotra,et al.  Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. , 2009, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[85]  D. Gozal,et al.  Platelet‐activating factor receptor‐deficient mice are protected from experimental sleep apnea‐induced learning deficits , 2004, Journal of neurochemistry.

[86]  L. Palmer,et al.  Cohort profile: the Western Australian Sleep Health Study , 2012, Sleep and Breathing.

[87]  E. van Cauter,et al.  Polycystic Ovary Syndrome and Obstructive Sleep Apnea. , 2008, Sleep medicine clinics.

[88]  M. Behan,et al.  Sex steroidal hormones and respiratory control , 2008, Respiratory Physiology & Neurobiology.

[89]  Francisco Lopez-Jimenez,et al.  Interactions between obesity and obstructive sleep apnea: implications for treatment. , 2010, Chest.

[90]  J. Hedner,et al.  Snoring and sleep apnoea in men: association with central obesity and hypertension. , 1993, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[91]  C. O'Donnell Metabolic consequences of intermittent hypoxia. , 2007, Advances in experimental medicine and biology.

[92]  M. Kraus,et al.  Sleep apnea in renal failure. , 1997, Advances in peritoneal dialysis. Conference on Peritoneal Dialysis.

[93]  J. Remmers Obstructive sleep apnea. A common disorder exacerbated by alcohol. , 1984, The American review of respiratory disease.

[94]  K. Hemminki,et al.  Obstructive sleep apnea syndrome in siblings: an 8-year Swedish follow-up study. , 2008, Sleep.

[95]  Y. Kitaura,et al.  Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress. , 2008, American journal of physiology. Heart and circulatory physiology.

[96]  S. Isono Obstructive Sleep Apnea of Obese Adults: Pathophysiology and Perioperative Airway Management , 2009, Anesthesiology.

[97]  E. Fletcher,et al.  highlighted topics Physiological and Genomic Consequences of Intermittent Hypoxia Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure , 2001 .

[98]  P. Nolan,et al.  Effects of sleep-wake state on the genioglossus vs.diaphragm muscle response to CO(2) in rats. , 2002, Journal of applied physiology.

[99]  S. Jones Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial , 2012 .

[100]  G. Semenza,et al.  Hypoxia‐inducible factor 1 mediates increased expression of NADPH oxidase‐2 in response to intermittent hypoxia , 2011, Journal of cellular physiology.

[101]  L. Kheirandish-Gozal,et al.  Obstructive sleep apnoea is associated with impaired pictorial memory task acquisition and retention in children , 2010, European Respiratory Journal.

[102]  S. Frangou Brain structural changes in mood disorders , 2009 .

[103]  R. Maestri,et al.  Night-to-night repeatability of measurements of nocturnal breathing disorders in clinically stable chronic heart failure patients , 2011, Sleep and Breathing.