Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, United States of America.
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, United States of America.
Exp Neurol. 2020 May;327:113212. doi: 10.1016/j.expneurol.2020.113212. Epub 2020 Jan 24.
Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.
睡眠碎片化是指睡眠-觉醒转换次数增加，而总睡眠时间没有减少。急性和慢性住院期间的睡眠碎片化已有充分记录，可导致儿童出现谵妄和记忆问题。在神经发育障碍中也经常观察到睡眠碎片化。然而，睡眠碎片化如何独立于疾病影响大脑发育和功能尚不清楚。我们假设，在其他方面健康的动物新生儿期的急性睡眠碎片化会导致神经炎症，并与认知发育异常有关。使用轨道摇床法在新生 3 天的新西兰白兔幼仔（碎片化组）中进行 72 小时的睡眠碎片化。为了控制母婴分离，假手术组与母兔分离，并在相同条件下保持分离状态，不进行睡眠碎片化。一个未经处理的对照组与母兔保持在一起。幼仔在碎片化后 2-3 周进行新物体识别和自发交替 T 迷宫测试，在碎片化后 3-50 天进行安乐死。睡眠碎片化导致海马体和皮质中小胶质细胞形态的急性和慢性变化，以及碎片化后 3、7 和 50 天促炎和抗炎细胞因子的 mRNA 表达的区域差异。碎片化幼仔的新物体识别能力受损，T 迷宫任务完成的潜伏期延长。尽管这些幼仔在 2 个月大时的睡眠结构正常化。结果表明，短暂的新生儿睡眠碎片化会导致大脑短期和长期的免疫改变，以及长期认知任务表现下降。
