Developmental differences in cortical and hippocampal vulnerability to intermittent hypoxia in the rat.
Obstructive sleep apnea is characterized by intermittent hypoxic events during sleep, and is associated with substantial neurocognitive morbidity, particularly in children. Intermittent hypoxia (IH) leads to increases in apoptosis in the cortex and hippocampus of the adult rat, peaking at 48 h of exposure. To examine whether the susceptibility to IH exhibits developmental differences, rats were exposed to 48 h of IH at ages 2, 5, 10, 15, 20, 25, 30, 60, and 120-day postnatally, and apoptosis was determined by terminal deoxy-nucleotidyl transferase-mediated in situ end labeling and immunohistochemical staining for single-stranded DNA. Although IH induced apoptosis at all postnatal ages, smaller increases were apparent in 2 and 5-day old (P < 0.01 vs. any other age) while peak apoptosis occurred at 10-25 days (P < 0.001 vs. 30, 60, and 120 days). We conclude that a unique window of vulnerability to IH is present in the cortex and hippocampus during post-natal maturation, and may underlie the high frequency of neurobehavioral deficits associated with obstructive sleep apnea in children.
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Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY 40202, USA. evelyne.gozal@louisville.edu
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D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D017209:Apoptosis / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology*; D004198:Disease Susceptibility; D006624:Hippocampus / Q000502:physiology*; D000860:Hypoxia / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values