Isoflurane Exposure Influence on Sleep Architecture in a Rat Model of Alzheimer's Disease.

Abstract

BACKGROUND: A clear understanding of how general anesthesia affects the brain in patients with Alzheimer disease will be crucial to optimize clinical care. We present results from laboratory investigations with a rat model used to study Alzheimer disease (TgF344-AD) to evaluate the effect of isoflurane anesthesia on the early recovery from anesthesia and postanesthesia sleep architecture in animals that exhibit mild symptoms of cognitive decline. METHODS: We used electroencephalogram (EEG) and electromyogram recordings to distinguish WAKE, NREM, and REM sleep in 8 rats from the transgenic model (AD) group and 7 age-matched control (AC) rats, 17 to 18 months of age. We evaluated the sleep architecture before and after a 1-hour exposure to 1.5% isoflurane. Therefore, we investigated the 12-hour active (lights-off) baseline period before anesthesia and the 5-hour recovery period after anesthesia emergence, and the following 12-hour lights-off period. RESULTS: The transgenic rats took longer to ambulate after the isoflurane challenge (mean [range] 1256 seconds [838-1565 seconds] vs 799 seconds [530-1125 seconds]; P = .038). There was no significant difference in the proportion of vigilance states during the 5-hour recovery period (ANOVA: WAKE, P = .081; NREM, P = .082; and REM, P = .993). In the first active period after isoflurane, the age-matched control rats showed increased sleep in the first active period after anesthesia compared to WAKE (ANOVA: P < .001), while the transgenic rats showed a higher overall WAKE duration (ANOVA: P < .001) and a more fragmented sleep behavior. CONCLUSIONS: Isoflurane affected the sleep architecture in the transgenic model for studying Alzheimer disease. The prolonged time to ambulation, the more fragmented SLEEP/WAKE behavior, and the relative hyperactivity compared to age-matched control rats may imply that Alzheimer disease diminishes the brain's dynamic range to adapt to altered levels of consciousness.