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

Abstract

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. 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. 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. 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.