0037 LONG-TERM BEHAVIORAL CONSEQUENCES OF NEONATAL SLEEP FRAGMENTATION

Abstract

Sleep fragmentation (SF) occurs in many disease states and frequently occurs in both the pediatric and adult intensive care units. However, it is unclear how sleep fragmentation in the absence of disease effects the neurochemical and behavioral development of the brain. In adults, SF results in daytime somnolence and a reduction in performance in attentional and vigilance tasks. Rodents who experience SF exhibit transient microglial activation and impaired hippocampal learning. The effects of SF on microglial activation and cytokine expression on the developing brain and long-term neurocognitive consequences have not been studied. Post-natal day 3 New Zealand White rabbit kits were assigned to one of three conditions: SF, sham, and control. The SF group was placed on an orbital shaker controlled by a timer to induce repetitive on/off cycling set at 100rpm on a 120s cycle (30s on, 90s off) for 72 hours. Shams were placed in an incubator for 72 hours, while the control group remained with the dam. Open field and behavioral milestone testing occurred before, during, and after active fragmentation. Fourteen days after fragmentation kits were challenged with a novel object recognition task. Three weeks after SF, a spontaneous alternation T-maze task was performed. Kits were sacrificed 3–50 days after the last day of fragmentation. Each hemisphere was processed separately for immunohistochemical evaluation and cytokine expression using rt-PCR. Microglial activation was associated with region specific modulations in cytokine production, and an upregulation of indoleamine 2,3-dioxygenase. Microglia continued to be activated in the SF group 50-days post-fragmentation. During active fragmentation and up to 24-hours post-fragmentation, SF kits displayed a hyperactive phenotype, with a higher velocity and traveled more distance in the open field. Long term, SF resulted in impaired novel object recognition and spent significantly more time completing the T-maze task. Early sleep fragmentation may lead to chronic immune dysregulation in the immature brain, subsequently leading to diminished long-term performance in cognitive tasks. HL110952-03, Society for Anesthesia and Sleep Medicine Research Grant.