Piecing together phenotypes of brain injury and dysfunction in obstructive sleep apnea

Frontiers in Neurology

Volumn OCT, Issue , 2012, Pages

  Veasey, Sigrid C ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Cognition; Cytokines; Endoplasmic reticulum; Hypoxia; Memory; NADPH oxidase

Indexed keywords

EID: 84870733937     PISSN: None     EISSN: 16642295     Source Type: Journal    
DOI: 10.3389/fneur.2012.00139     Document Type: Article

References (101)

1. Alchanatis, M., Deligiorgis, N., Zias, N., Amfilochiou, A., Gotsis, E., and Karakatsani, A. et al. (2004). Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spec-troscopy study. Eur. Respir. J. 24, 980-986.
2. Almendros, I., Farre, R., Planas, A. M., Torres, M., Bonsignore, M., Nava-jas, D., et al. (2011). Tissue oxy-genation in brain, muscle, and fat in a rat model of sleep apnea: differential effect of obstructive apneas and intermittent hypoxia. Sleep 34, 1127-1133.
3. Aloia, M. S., Arnedt, J. T., Smith, L., Skrekas, J., Stanchina, M., and Mill-man, R. P. (2005). Examining the construct of depression in obstructive sleep apnea syndrome. Sleep Med. 6, 115-121.
4. Antic, N. A., Catcheside, P., Buchan, C., Hensley, M., Naughton, M., Rowland, L. S., et al. (2011). The effect of CPAP in normalizing daytime sleepiness, quality of life, and neurocognitive function in patients with moderate to severe OSA. Sleep 34, 111-119.
5. Ayalon, L., Ancoli-Israel, S., and Drum-mond, S. P. (2009a). Altered brain activation during response inhibition in obstructive sleep apnea. J. Sleep Res. 18,204-208.
6. Ayalon, L., Ancoli-Israel, S., Aka, A. A., McKenna, B. S., and Drummond, S. P. (2009b). Relationship between obstructive sleep apnea severity and brain activation during a sustained attention task. Sleep 32, 373-381.
7. Ayalon, L., Ancoli-Israel, S., and Drummond, S. P. (2010). Obstructive sleep apnea and age: a double insult to brain function? Am. J. Respir. Crit. Care Med. 182, 413-419.
8. Balfors, E. M., and Franklin, K. A. (1994). Impairment of cerebral perfusion during obstructive sleep apneas. Am. J. Respir. Crit. Care Med. 150(6 Pt 1), 1587-1591.
9. Barnes, M. E., Gozal, D., and Molfese, D. L. (2012).Attentionin children with obstructive sleep apnoea: an event-related potentials study. Sleep Med. 13,368-377.
10. Bartlett, D. J., Rae, C, Thompson, C. H., Byth, K., Joffe, D. A., Enright, T., et al. (2004). Hippocampal area metabolites relate to severity and cognitive function in obstructive sleep apnea. Sleep Med. 5, 593-596.
11. Bhattacharjee, R., Kheirandish-Gozal, L., Pillar, G., and Gozal, D. (2009). Cardiovascular complications of obstructive sleep apnea syndrome: evidence from children. Prog. Car-diovasc. Dis. 51,416-433.
12. Bourke, R., Anderson, V., Yang, J. S., Jackman, A. R., Killedar, A., Nixon, G. M., et al. (2011a). Cognitive and academic functions are impaired in children with all severities of sleep-disordered breathing. Sleep Med. 12, 489-496.
13. Bourke, R. S., Anderson, V., Yang, J. S., Jackman, A. R., Killedar, A., Nixon, G. M., et al. (2011b). Neurobehav-ioral function is impaired in children with all severities of sleep disordered breathing. Sleep Med. 12,222-229.
14. Burckhardt, I. C., Gozal, D., Dayyat, E., Cheng, Y., Li, R. C., Goldbart, A. D., et al. (2008). Green tea cat-echin polyphenols attenuate behavioral and oxidative responses to intermittent hypoxia. Am. J. Respir. Crit. Care Med. 177, 1135-1141.
15. Canessa, N., Castronovo, V., Cappa, S. E, Aloia, M. S., Marelli, S., Falini, A., et al. (2011). Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am. J. Respir. Crit. Care Med. 183, 1419-1426.
16. Cardenas, V. A., Chao, L. L., Studholme, C., Yaffe, B. L., Miller, C., Madison, S. T., et al. (2011). Brain atrophy associated with baseline and longitudinal measures of cognition. Neurobiol. Aging 32, 572-580.
17. Carlson, B. W., Neelon, V. J., Carlson, J. R., Hartman, M., and Bli-wise, D. L. (2011). Cerebral oxygena-tion in wake and during sleep and its relationship to cognitive function in community-dwelling older adults without sleep disordered breathing. J. Gerontol. A Biol. Sci. Med. Sci. 66, 150-156.
18. Cho, J. G., Witting, P. K., Verma, M., Wu, B. J., Shanu, A., Kairaitis, K., et al. (2011). Tissue vibration induces carotid artery endothelial dysfunction: a mechanism linking snoring and carotid atherosclerosis? Sleep 34, 751-757.
19. Dayyat, E., Kheirandish-Gozal, L., Sans Capdevila, O., Maarafeya, M. M., and Gozal, D. (2009). Obstructive sleep apnea in children: relative contributions of body mass index and adenotonsillar hypertrophy. Chest 136, 137-144.
20. Dempsey, J. A., Veasey, S. C., Morgan, B. J., and O'Donnell, C. P. (2010). Pathophysiology of sleep apnea. Physiol. Rev. 90, 47-112.
21. Douglas, R. M., Ryu, J., Kanaan, A., del Carmen Rivero, M., Dugan, L. L., Haddad, G. G., et al. (2010). Neu-ronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction. Am. I Physiol. Cell Physiol. 298, C1594-C1602.
22. Dziewas, R., Schilling, M., Engel, P., Boentert, M., Hor, H., Okegwo, A., et al. (2007). Treatment for obstructive sleep apnoea: effect on peripheral nerve function. J. Neurol. Neurosurg. Psychiatr. 78, 295-297.
23. El-Sherbini, A. M., Bediwy, A. S., and El-Mitwalli, A. (2011). Association between obstructive sleep apnea (OSA) and depression and the effect of continuous positive airway pressure (CPAP) treatment. Neuropsy-chiatr. Dis. Treat. 7, 715-721.
24. Engleman,H.,and Joffe,D. (1999).Neu-ropsychological function in obstructive sleep apnoea. Sleep Med. Rev. 3, 59-78.
25. Engleman, H. M., and Douglas, N. J. (2004). Sleep. 4: sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome. Thorax 59, 618-622.
26. Fanfulla, F., Malaguti, S., Montagna, T., Salvini, S., Bruschi, C., Crotti, P., et al. (2000). Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement. Sleep 23, 775-781.
27. Fjell, A. M., Walhovd, K. B., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Holland, D., et al. (2009). One-year brain atrophy evident in healthy aging. J. Neurosci. 29, 15223-15231.
28. Foster, G. E., Hanly, P. J., Ostrowski, M., and Poulin, M. J. (2009). Ventila-tory and cerebrovascular responses to hypercapnia in patients with obstructive sleep apnoea: effect of CPAP therapy. Respir. Physiol. Neurobiol. 165,73-81.
29. Fregosi, R. F., Quan, S. F., Kaemingk, K. L., Morgan, W. J., Goodwin, J. L., Cabrera, R., and Gmitro, A. (2003). Sleep-disordered breathing, pharyn-geal size and soft tissue anatomy in children. J. Appl. Physiol. 95, 2030-2038.
30. Furtner, M., Staudacher, M., Frauscher, B., Brandauer, E., Rojas, M. M., Gschliesser,V.,etal. (2009). Cerebral vasoreactivity decreases overnight in severe obstructive sleep apnea syndrome: a study of cerebral hemody-namics. Sleep Med. 10, 875-881.
31. Gazdzinski, S., Kornak, J., Weiner, M. W., and Meyerhoff, D. J. (2008). Body mass index and magnetic resonance markers of brain integrity in adults. Ann. Neurol. 63, 652-657.
32. Gazdzinski, S., Millin, R., Kaiser, L. G., Durazzo, T. C., Mueller, S. G., Weiner, M. W., et al. (2010). BMI and neuronal integrity in healthy, cognitively normal elderly: a proton magnetic resonance spectroscopy study. Obesity (Silver Spring) 18, 743-748.
33. Gozal, D., Daniel, J. M., and Dohanich, G. P. (2001). Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J. Neurosci. 21, 2442-2450.
34. Gozal, D., and Kheirandish-Gozal, L. (2007). Neurocognitive and behavioral morbidity in children with sleep disorders. Curr. Opin. Pulm. Med. 13, 505-509.
35. Gozal, D., and Kheirandish-Gozal, L. (2009). Obesity and excessive daytime sleepiness in prepubertal children with obstructive sleep apnea. Pediatrics 123, 13-18.
36. Gozal, D., Nair, D., and Goldbart, A. D. (2010). Physical activity atten uates intermittent hypoxia-induced spatial learning deficits and oxida tive stress. Am. J. Respir. Crit. Care Med. 182, 104-112.
37. Guilleminault, C., Eldridge, F. L., Simmon, E B., and Dement, W C. (1975). Sleep apnea syndrome. Can it induce hemodynamic changes? WestJ. Med. 123, 7-16.
38. Hajak, G., Klingelhofer, J., Schulz-Varszegi, M., Sander, D., and Ruther, E. (1996). Sleep apnea syndrome and cerebral hemodynamics. Chest 110, 670-679.
39. Halbower, A. C., Degaonkar, M., Barker, P. B., Earley, C. J., Marcus, C. L., Smith, P. L., et al. (2006). Childhood obstructive sleep apnea associates with neuropsy-chological deficits and neuronal brain injury. PLoS Med. 3, e301. doi:10.1371/journal.pmed.0030301
40. Heinzer, R. C., Pellaton, C., Rey, V., Ros-setti, A. O., Lecciso, G., Haba-Rubio, J., et al. (2012). Positional therapy for obstructive sleep apnea: an objective measurement of patients' usage and efficacy at home. Sleep Med. 13, 425-428.
41. Hendricks, J. C., Kline, L. R., Koval-ski, R. J., O'Brien, J. A., Morrison, A. R., and Pack, A. I. (1987). The English bulldog: a natural model of sleep-disordered breathing. J. Appl. Physiol. 63,1344-1350.
42. Hong, S., Flashner, B., Chiu, M., ver Hoeve, E., Luz, S., and Bhatnagar, S. (2012). Social isolation in adolescence alters behaviors in the forced swim and sucrose preference tests in female but not in male rats. Physiol. Behav. 105,269-275.
43. Jenkinson, C., Davies, R. J., Mullins, R., and Stradling, J. R. (1999). Comparison of therapeutic and sub therapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 353,2100-2105.
44. Kales, A., Caldwell, A. B., Cadieux, R. J., Vela-Bueno, A., Ruch, L. G., and Mayes, S. D. (1985). Severe obstructive sleep apnea - II: associated psychopathology and psychosocial consequences. J. Chronic Dis. 38, 427-434.
45. Kamba, M., Inoue, Y., Higami, S., Suto, Y., Ogawa, T., and Chen, W. (2001). Cerebral metabolic impairment in patients with obstructive sleep apnoea: an independent association of obstructive sleep apnoea with white matter change. J. Neurol. Neurosurg. Psychiatr. 71, 334-339.
46. Kamba, M., Suto, Y., Ohta, Y., Inoue, Y., and Matsuda, E. (1997). Cerebral metabolism in sleep apnea. Evaluation by magnetic resonance spectroscopy. Am. J. Respir. Crit. Care Med. 156,296-298.
47. Kent, B. D., Ryan, S., and McNi-cholas, W T. (2010). The genetics of obstructive sleep apnoea. Curr. Opin. Pulm. Med. 16, 536-542.
48. Lau, E. Y., Eskes, G. A., Morrison, D. L., Rajda, M., and Spurr, K. E (2010). Executive function in patients with obstructive sleep apnea treated with continuous positive airway pressure. J. Int. Neuropsychol. Soc. 16, 1077-1088.
49. Lavie,L. (2009). Oxidative stress-a unifying paradigm in obstructive sleep apnea and comorbidities. Prog. Car-diovasc. Dis. 51,303-312.
50. Lee, S. A., Amis, T. C., Byth, K., Lar-cos, G., Kairaitis, K., Robinson, T. D., et al. (2008). Heavy snoring as a cause of carotid artery atherosclerosis. Sleep 31, 1207-1213.
51. Li, R. C., Row, B. W., Gozal, E., Kheiran-dish, L., Brittian, K. R., and Guo, S. Z. et al. (2003). Cyclooxygenase 2 and intermittent hypoxia-induced spatial deficits in the rat. Am. J. Respir. Crit. Care Med. 168,469-475.
52. Li, R. C., Row, B. W., Kheirandish, L., Brittian, K. R., Gozal, E., Guo, S. Z., et al. (2004). Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat. Neurobiol. Dis. 17,44-53.
53. Li,Y.,andVeasey,S. C. (2012).Neurobi-ology and neuropathophysiology of obstructive sleep apnea. Neuromole-cularMed. 14, 168-179.
54. Lu, Z., Tang, X., and Huang, X. (1998). Phrenic nerve conduction and diaphragmatic motor evoked potentials: evaluation of respiratory dysfunction. Chin. Med. J. (Engl.) 111,496-499.
55. Macey, P. M., Henderson, L. A., Macey, K. E., Alger, J. R., Frysinger, R. C, Woo, M. A., et al. (2002). Brain morphology associated with obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 166, 1382-1387.
56. Macey, P. M., Kumar, R, Woo, M. A., Valladares, E. M., Yan-Go, F. L., and Harper, R. M. (2008). Brain structural changes in obstructive sleep apnea. Sleep 31, 967-977.
57. Mathieu, A., Mazza, S., Decary, A., Massicotte-Marquez, J., Petit, D., Gosselin, N., et al. (2008). Effects of obstructive sleep apnea on cognitive function: a comparison between younger and older OSAS patients. Sleep Med. 9, 112-120.
58. Mayer, P., Dematteis, M., Pepin, J. L., Wuyam, B., Veale, D., Vila, A., et al. (1999). Peripheral neuropathy in sleep apnea. A tissue marker of the severity of nocturnal desaturation. Am. J. Respir. Crit. Care Med. 159, 213-219.
59. McCoy, J. G., McKenna, J. T., Connolly, N. P., Poeta, D. L., Ling, L., McCarley, R. W., et al. (2010). One week of exposure to intermittent hypoxia impairs attentional set-shifting in rats. Behav. Brain Res. 210, 123-126.
60. Michielse, S., Coupland, N., Camicioli, R., Carter, R., Seres, P., Sabino, J., et al. (2010). Selective effects of aging on brain white matter microstruc-ture: a diffusion tensor imaging tractography study. Neuroimage 52, 1190-1201.
61. Morgan, B. J., Reichmuth, K. J., Peppard, P. E., Finn, L., Barczi, S. R., Young, T., et al. (2010). Effects of sleep-disordered breathing on cerebrovas-cular regulation: a population-based study. Am. J. Respir. Crit. Care Med. 182,1445-1452.
62. Morrell, M. J., Jackson, M. L., Twigg, G. L., Ghiassi, R., McRobbie, D. W., and Quest, R. A. et al. (2010). Changes in brain morphology in patients with obstructive sleep apnoea. Thorax 65, 908-914.
63. Morrell, M. J., McRobbie, D. W., Quest, R. A., Cummin, A. R., Ghiassi, R., and Corfield, D. R. (2003). Changes in brain morphology associated with obstructive sleep apnea. Sleep Med. 4,451-454.
64. Nair, D., Zhang, S. X., Ramesh, V., Hakim, F., Kaushal, N., Wang, Y., et al. (2011). Sleep fragmentation induces cognitive deficits via nicoti-namide adenine dinucleotide phosphate oxidase-dependent pathways in mouse. Am. J. Respir. Crit. Care Med. 184,1305-1312.
65. Neuzeret, P. C., Gormand, F., Reix, P., Parrot, S., Sastre, J. P., Buda, C., et al. (2011). A new animal model of obstructive sleep apnea responding to continuous positive airway pressure. Sleep 34, 541-548.
66. Nyberg, L., Salami, A., Andersson, M., Eriksson, J., Kalpouzos, G., Kauppi, K. et al. (2010). Longitudinal evidence for diminished frontal cortex function in aging. Proc. Natl. Acad. Sci. U. S. A. 107, 22682-22686.
67. O'Brien, J. L., O'Keefe, K. M., LaVio-lette, P. S., DeLuca, A. N., Blacker, D., Dickerson, B. C., et al. (2010). Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology 74, 1969-1976.
68. O'Donoghue, F. J., Briellmann, R. S., Rochford, P. D., Abbott, D. F., Pell, G. S., Chan, C. H. P., et al. (2005). Cerebral structural changes in severe obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 171, 1185-1190.
69. Park, J. G., Ramar, K., and Olson, E. J. (2011). Updates on definition, consequences, and management of obstructive sleep apnea. Mayo Clin. Proc. 86, 549-554; quiz 54-55.
70. Patel, S. R., White, D. P., Malhotra, A., Stanchina, M. L., and Ayas, N. T. (2003). Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch. Int. Med. 163, 565-571.
71. Peppard, P. E. (2009). Is obstructive sleep apnea a risk factor for hypertension? Differences between the Wisconsin Sleep Cohort, and the Sleep Heart Health Study. J. Clin. Sleep Med. 5,404-405.
72. Pizza, F., Biallas, M., Wolf, M., Werth, E., andBassetti, C. L. (2010). Nocturnal cerebral hemodynamics in snorers and in patients with obstructive sleep apnea: a near-infrared spectroscopy study. Sleep 33, 205-210.
73. Prabhakar, N. R., Kumar, G. K., and Nanduri, J. (2010). Intermittent hypoxia augments acute hypoxic sensing via HIF-mediated ROS. Respir. Physiol. Neurobiol. 174, 230-234.
74. Punjabi, N. M. (2008). The epidemiology of adult obstructive sleep apnea. Proc. Am. Thorac. Soc. 5, 136-143.
75. Ray, A. D., Magalang, U. J., Michlin, C. P., Ogasa, T., Krasney, J. A., Gosselin, L. E., et al. (2007). Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R372-R378.
76. Redline, S., Yenokyan, G., Gottlieb, D. J., Shahar, E., O'Connor, G. T., Resnick, H. E., et al. (2010). Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am. I Respir. Crit. Care Med. 182, 269-277.
77. Reeves, S. R., and Gozal, D. (2004). Platelet-activating factor receptor modulates respiratory adaptation to long-term intermittent hypoxia in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R369-R374.
78. Remmers, J. E., deGroot, W. J., Sauer-land, E. K., and Anch, A. M. (1978). Pathogenesis of upper airway occlusion during sleep. J. Appl. Physiol. 44, 931-938.
79. Ryan, C. M., Bayley, M., Green, R., Murray, B. J., and Bradley, T. D. (2011). Influence of continuous positive airway pressure on outcomes of rehabilitation in stroke patients with obstructive sleep apnea. Stroke 42, 1062-1067.
80. Sassani, A., Findley, L. J., Kryger, M., Goldlust, E., George, C., and Davidson, T. M. (2004). Reducing motor-vehicle collisions, costs, and fatalities by treating obstructive sleep apnea syndrome. Sleep 27, 453-458.
81. Saunamaki, T., Himanen, S. L., Polo, O., and Jehkonen, M. (2010). Executive dysfunction and learning effect after continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome. Eur. Neu-rol. 63,215-220.
82. Scharf, S. M., Graver, L. M., and Balaban, K. (1992). Cardiovascular effects of periodic occlusions of the upper airways in dogs. Am. Rev. Respir. Dis. 146,321-329.
83. Schulze, E. T., Geary, E. K., Susmaras, T. M., Paliga, J. T., Maki, P. M., and Little, D. M. (2011). Anatomical correlates of age-related working memory declines. J. Aging Res. 2011, 606871.
84. Sellbom, K. S., and Gunstad, J. (2012). Cognitive function and decline in obesity. J. Alzheimers Dis. 30 (Suppl 2),S89-S95.
85. Sforza, E., Roche, F., Thomas-Anterion, C., Kerleroux, J., Beauchet, O., Celle, S., et al. (2010). Cognitive function and sleep related breathing disorders in a healthy elderly population: the SYNAPSE study. Sleep 33, 515-521.
86. Skatrud, J. B., Henke, K. G., and Dempsey, J. (1990). A sleep-induced apneic threshold. Prog. Clin. Biol. Res. 345, 191-199; discussion 9-200.
87. Taki, Y., Kinomura, S., Sato, K., Goto, R., Kai, W., Kawashima, R., et al. (2011a). Correlation between gray/white matter volume and cognition in healthy elderly people. Brain Cogn. 75,170-176.
88. Taki, Y., Kinomura, S., Sato, K., Goto, R., Kai, W., Kawashima, R., et al. (2011b). Correlation between degree of white matter hyperinten-sities and global gray matter volume decline rate. Neuroradiology 53, 397-403.
89. Teipel, S. J., Meindl, T., Wagner, M., Stieltjes, B., Reuter, S., Hauenstein, K. H., et al. (2010). Longitudinal changes in fiber tract integrity in healthy aging and mild cognitive impairment: a DTI follow-up study. J. Alzheimers Dis. 22, 507-522.
90. Thomas, R. J., Rosen, B. R., Stern, C. E., Weiss, J. W., and Kwong, K. K. (2005). Functional imaging of working memory in obstructive sleep-disordered breathing. J. Appl. Physiol. 98, 2226-2234.
91. Tonon, C., Vetrugno, R., Lodi, R., Gallassi, R., Provini, F., Iotti, S., et al. (2007). Proton magnetic resonance spectroscopy study of brain metabolism in obstructive sleep apnoea syndrome before and after continuous positive airway pressure treatment. Sleep 30, 305-311.
92. Twigg, G. L., Papaioannou, I., Jackson, M., Ghiassi, R., Shaikh, Z., Jaye, J., et al. (2010). Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory. Am. J. Respir. Crit. Care Med. 182, 98-103.
93. Veasey, S. C., Davis, C. W., Fenik, P., Zhan, G., Hsu, Y.-J., Pratico, D., et al. (2004). Long-term intermittent hypoxia in mice: protracted hyper-somnolence with oxidative injury to sleep-wake brain regions. Sleep 27, 194-201.
94. Vernet, C., Redolfi, S., Attali, V., Konofa, E., Brion, A., Frija-Orvoen, E., et al. (2011). Residual sleepiness in obstructive sleep apnoea: phenotype and related symptoms. Eur. Respir. J. 38,98-105.
95. Vgontzas, A. N., Tan, T. L., Bixler, E. O., Martin, L. F., Shubert, D., and Kales, A. (1994). Sleep apnea and sleep disruption in obese patients. Arch. Int. Med. 154,1705-1711.
96. Weaver, T. E., and Sawyer, A. M. (2010). Adherence to continuous positive airway pressure treatment for obstructive sleep apnoea: implications for future interventions. Indian J. Med. Res. 131, 245-258.
97. Young, T., Palta, M., Dempsey, J., Skatrud, J., Weber, S., and Badr, S. (1993). The occurrence of sleep-disordered breathing among middle-aged adults. N. Engl. J. Med. 328, 1230-1235.
98. Zhan, G., Fenik, P., Pratico, D., and Veasey, S. C. (2005a). Inducible nitric oxide synthase in long-term intermittent hypoxia: hypersom-nolence and brain injury. Am. J. Respir. Crit. Care Med. 171, 1414-1420.
99. Zhan, G, Serrano F, Fenik P, Hsu, R., Kong, L., Pratico, D., et al. (2005b). NADPH oxidase mediates hypersomnolence and brain oxida-tive injury in a murine model of sleep apnea. Am. J. Respir. Crit. Care Med. 172,921-929.
100. Zhang, X., Ma, L., Li, S., Wang, Y., and Wang, L. (2011). A functional MRI evaluation of frontal dysfunction in patients with severe obstructive sleep apnea. Sleep Med. 12, 335-340.
101. Zhu, Y., Fenik, P., Zhan, G., Mazza, E., Kelz, M., Aston-Jones, G., et al. (2007). Selective loss of catecholaminergic wake active neurons in a murine sleep apnea model. J. Neurosci. 27,10060-10071