Published ahead of print on February 25, 2003, doi:10.1164/rccm.200209-1050OC
American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1548-1553, (2003)
© 2003 American Thoracic Society
Intermittent Hypoxia Is Associated with Oxidative Stress and Spatial Learning Deficits in the Rat
Barry W. Row,
Rugao Liu,
Wei Xu,
Leila Kheirandish and
David Gozal
Department of Pediatrics, Kosair Children's Hospital Research Institute; and Department of Pharmacology & Toxicology, University of Louisville, Louisville, Kentucky
Correspondence and requests for reprints should be addressed to David Gozal, M.D., Kosair Children's Hospital Research Institute, University of Louisville, Baxter Biomedical Research Building, Suite 321, 570 South Preston Street, Louisville, KY 40202. E-mail: david.gozal{at}louisville.edu
In the adult rat, exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with neurobehavioral impairments and increased apoptosis in the hippocampal CA1 region and cortex. We hypothesized that the episodic hypoxic-reoxygenation cycles of IH would induce oxidant stress, and the latter may underlie the IH-associated spatial learning and retention deficits. Adult male rats were therefore exposed to IH (90-second alternations of 10% oxygen and 21% oxygen) or room air (RA) for 7 days, and received twice-daily injections of either 3 mg/kg of the antioxidant PNU-101033E (PNU) or vehicle (V). Rats were then trained in a standard place-training task in the water maze. V-IH displayed significant impairments of spatial learning in the water maze, which were attenuated by PNU-101033E. Post hoc analyses further revealed that V-IH had significantly longer latencies and pathlengths to locate the hidden platform than PNU-IH, V-RA, or PNU-RA, indicating that PNU-101033E treatment reduced the behavioral impairments associated with IH. In addition, treatment with PNU-101033E markedly attenuated the increase in lipid peroxidation, and isoprostane concentrations associated with exposure to IH. Collectively, these findings indicate that the IH exposure is associated with increased oxidative stress, which is likely to play an important role in the behavioral impairments observed in a rodent model of sleep-disordered breathing.
Key Words: intermittent hypoxia • sleep apnea • spatial learning • oxidative stress • sleep-disordered breathing
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|
|
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|
|
|
|
|
|
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97(3):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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January 1, 2007;
4(1):
121 - 126.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Pack
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January 1, 2006;
173(1):
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[Abstract]
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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98(6):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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170(6):
581 - 582.
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|
|
|
|
|
|
|
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September 15, 2004;
170(6):
665 - 672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Sforza, J. Haba-Rubio, F. De Bilbao, T. Rochat, and V. Ibanez
Performance vigilance task and sleepiness in patients with sleep-disordered breathing
Eur. Respir. J.,
August 1, 2004;
24(2):
279 - 285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
254 - 264.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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January 15, 2004;
169(2):
277 - 287.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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December 1, 2003;
42(6):
1130 - 1136.
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|
|
|
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