Sleep Restriction Impairs Blood-Brain Barrier Function
Sleep Restriction Impairs Blood-Brain Barrier Function
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DOI：
10.1523/jneurosci.2111-14.2014
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发表时间：
2014-10-29
影响因子：
5.3
通讯作者：
Pan, Weihong
中科院分区：
文献类型：
--
作者：
He, Junyun;Hsuchou, Hung;Pan, Weihong
血脑屏障（BBB）是大脑和外周循环之间一个巨大的调节和交换界面。我们认为血脑屏障的改变参与了慢性睡眠限制（CSR）受试者大脑中的许多病理生理过程。为了实现模仿人类睡眠缺失的常见模式的CSR，我们通过连续一周的睡眠记录来量化小鼠睡眠中断的新程序。然后，我们验证了CSR损害微血管功能的假设。CSR不仅降低了血脑屏障脑微血管中内皮和诱导型一氧化氮合酶、内皮素1和葡萄糖转运蛋白的表达，而且还降低了脑对2-脱氧葡萄糖的摄取。几个紧密连接蛋白的表达也降低，而环氧化酶-2的表达水平升高。这与血脑屏障对小示踪剂荧光素钠和生物素的细胞旁通透性增加相一致。6 d的CSR足以损害血脑屏障的结构和功能，尽管在24小时的恢复性睡眠后，细胞旁通透性的增加恢复到基线。这不仅在神经科学研究中值得注意，而且在公共卫生政策和临床实践中也值得注意。
The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice.