Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-α in aging.
Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-α in aging.
复制标题
睡眠碎片化和败血症对衰老过程中血脑屏障的完整性和肿瘤坏死因子-α 的运输有不同的影响。
DOI：
10.1016/j.bbi.2015.07.023
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Banks,WilliamA
中科院分区：
文献类型：
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作者：
Opp,MarkR;George,Amrita;Ringgold,KristynM;Hansen,KimM;Bullock,KristinM;Banks,WilliamA
导致老年人易患严重疾病的因素是多种多样的、复杂的，而且还没有得到很好的理解。脓毒症被认为是一种典型的老年疾病，因为严重脓毒症的发病率和死亡率在老年人和最年长的老年人中增加。衰老与睡眠质量和数量的巨大变化有关，随着年龄的增长，睡眠越来越分散。在健康的成年人中，睡眠中断会诱发炎症。衰老和睡眠失调的多个方面相互作用的神经免疫机制。肿瘤坏死因子-α (TNF)是一种参与睡眠调节和神经免疫过程的细胞因子，它通过血脑屏障（BBB）对中枢神经系统施加一些影响。在这项研究中，我们研究了败血症、睡眠破碎和衰老对血脑屏障破坏和TNF转运到大脑的影响。我们使用盲肠结扎和穿刺（CLP）模型的脓毒症的年轻和老年小鼠，无论是不受干扰或睡眠中断。随着年龄的增长，败血症和睡眠中断具有双重作用：败血症在年轻小鼠中破坏血脑屏障并增加TNF转运，但在老年小鼠中没有，而在老年小鼠中，睡眠中断破坏血脑屏障并增加TNF转运，但在年轻小鼠中没有。结合睡眠分裂和CLP对血脑屏障参数的影响并不比单独使用这两种方法产生更大的影响。这些结果表明，睡眠断裂和败血症改变血脑屏障功能的机制彼此根本不同，随着年龄的增长，机体对这些损害的反应发生了重大变化。
The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interactvianeuroimmune mechanisms. Tumor necrosis factor-α (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood–brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism’s responses to those insults occurs with aging.