Introduction: It is known that the obstructive sleep apnea (OSA) would cause neuropsychological effects including impaired memory, attention, and executive dysfunction due to OSA-related intermittent hypoxia (IH). The aim of this study was to produce the model of intermittent chronic hypoxic brain condition in rats and find the cut-off value of spontaneous recovery according to duration of hypoxic exposure.
Method: Fifty male Sprague-Dawley 8-week-old rats, weighing 300±50 g, were subjected into five groups; control group (A, n=10), 1 hour/day hypoxia exposure group (B, n=10), 2 hours/day hypoxia exposure group (C, n=10), 4 hours/day hypoxia exposure group (D, n=10) and 8 hours/day hypoxia exposure group (E, n=10). All rats were exposed in hypoxic chamber containing 10% oxygen for 5 days.
Neurocognitive function was evaluated with the Morris water maze test after 5 days hypoxic exposure. The PET brain images were acquired by the preclinical PET-CT scanner for evaluating the activity of brain metabolism. And all rats were put into normal circumstances. After 5 days, Morris water maze test and PET-CT was done for evaluation of spontaneous recovery of brain function. Western blot analysis examined brain-derived neurotrophic factor (BDNF).
Results: After exposure to 10% O2 for 1 week, escape latencies was measured as 59.24±44.47 sec in group A, 58.34±43.28 sec in group B, 74.42±38.23 sec in group C, 50.78±33.22 sec in group D, and 56.51±30.28 sec in group E on the Morris water maze test. Then, all rats were put into normal circumstances for 1 week. Escape latency was 43.61±31.41 sec in group A, 53.25±30.65 sec in group B, 62.42±34.22 sec in group C, 55.67±29.85 sec in group D, and 66.80±29.56 sec in group E (Fig 1). Mean SUV was 0.576±0.010 mCi/mL in group A, 1.204±0.152 mCi/mL in group B, 0.692±0.020 mCi/mL in group C, 0.992±0.124 mCi/mL in group D and 1.002±0.003 mCi/mL in group E. After normal circumstances. mean SUV was 0.456±0.013 mCi/mL in group A, 0.923±0.266 mCi/mL in group B, 0.859±0.010 mCi/mL in group C, 1.070±0.353 mCi/mL in 4 group D and 0.776±0.265 mCi/mL in group E (Fig 2). Western blot analysis demonstrated BDNF proteins were markedly expressed in group C (Fig 3).
Conclusions: It showed that the spontaneous recovery after intermittent chronic hypoxic brain condition in rats may be expected under 4 hours/day hypoxic exposure containing 10 % oxygen in this study. |
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Neurobehavioral test with Morris water maze. Escape latency was not statistically significant after 1 week induction of hypoxic brain injury and after exposure to the normal circumstances for 1 week. However, the escape latency was increased in the group with an exposure time of 4 hours/day and 8 hours/day group.
Brain Metabolism using small animal PET/CT imaging. No statistical differences were observed among groups at each time point. However, the mean SUV was decreased in the group with an exposure time of 8 hours/day.
Western blot for BDNF. Expression of BDNF protein was stronger in 2 hours/day group than other groups.
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