No abstract

No abstract

Introduction Cognitive and spatial dysfunction is common among patients with obstructive sleep apnea (OSA). The cause of these abnormalities may be related to the effects of hypoxic damage in the brain during sleep. Here we report a rodent model for chronic intermittent hypoxia (CIH) that examines spatial performance tasks via a Barnes Maze paradigm. We hypothesized that increased severity of CIH yields decreased cognitive and spatial performance. Methods Three groups of rats were subject to varying levels of hypoxia conditions: sham (21% oxygen; n = 19), moderate (11% oxygen; n = 14), and severe (6% oxygen; n = 21). To deliver hypoxia, rats were exposed to three-minute cycles of oxygen between 21% and condition-specific nadir oxygen for 12 hours daily (during sleep) in specialized chambers. Barnes maze testing was performed at 0, 1, 2, and 3 months. Rats were placed on a circular platform with 19 shallow holes and one deeper target hole to escape the noxious sound. Each month, rats had 3 minutes to find the target hole in four daily trials over four consecutive days. Average maze completion time on day 4 was recorded. Results Rats from the three hypoxia groups did not differ significantly in mean maze completion time at baseline (0 months). Throughout the three months of exposure to hypoxic conditions, maze completion time on day 4 did not differ significantly from baseline for sham rats. However, by month 3, rats exposed to severe hypoxic conditions had a significantly larger percent increase from baseline compared to sham rats (p = 0.0358). Conclusion Our findings indicate that rats undergoing intermittent hypoxia perform worse than normoxic rats in spatial performance tasks. These data suggest there is a relationship between CIH and cognitive/spatial impairment. Support Funded by NIH P01 HL094307

Introduction Patients with obstructive sleep apnea (OSA) commonly exhibit grey and white matter loss, which may be related to hypoxic damage in the brain during sleep. Our preliminary data demonstrated lower values of cerebral metabolic rate of oxygen (CMRO2) consumption in apneics versus controls. As such, reduced CMRO2 may be an important contributor to the neurologic consequences of OSA. Here we report a rodent model for chronic intermittent hypoxia (CIH) to quantify effects on CMRO2 consumption. We hypothesized that increased severity of CIH results in decreased CMRO2 levels. Methods Three groups of rats were subject to varying levels of hypoxia: sham (21% oxygen; n = 19), moderate (11% oxygen; n = 14), and severe (6% oxygen; n = 21). To deliver hypoxia, rats were exposed to three-minute cycles of oxygen between 21% and condition-specific nadir O2 for 12 hours daily during their sleep cycle. CMRO2 values were measured with MRI techniques, performed on anesthetized rats before and after 3 months exposure to CIH. Results Rats from the three hypoxia groups did not differ significantly in CMRO2 values at baseline (0 months). After 3 months of exposure to hypoxic conditions, there was a trending difference (p=0.0726) in percent change from baseline between severely hypoxic (-35.3%) and sham (+12.3%) rats. Moderately hypoxic rats demonstrated an intermediate decrease from baseline after 3 months (-19.0%). Conclusion Our findings suggest that increased severity of intermittent hypoxia yields a dose-response decrease in brain oxygen consumption. Our data add to the growing body of evidence on the relationship between obstructive sleep apnea and hypoxic damage in the brain, suggesting that CMRO2 levels may be an indicator of the neurologic consequences of OSA. Support Funded by NIH P01 HL094307