Urinary Catheterization Induces Delirium-Like Behavior Through Glucose Metabolism Impairment in Mice.
Urinary Catheterization Induces Delirium-Like Behavior Through Glucose Metabolism Impairment in Mice.
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DOI：
10.1213/ane.0000000000006008
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发表时间：
2022-09-01
影响因子：
5.7
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中科院分区：
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谵妄是一种急性精神错乱状态，与不良反应有关，包括阿尔茨海默病的发展。然而，谵妄的病因学和潜在机制在很大程度上仍有待确定。许多患者有导尿术（UC），UC与谵妄有关。然而，UC相关性谵妄的因果关系和潜在的机制在很大程度上仍然未知。因此，我们在小鼠中建立了无尿路感染的UC动物模型，并确定UC是否可以在小鼠中诱导谵妄样行为以及这些作用的潜在机制。成年雌性小鼠（16周龄）在短暂异氟烷麻醉下放置UC。使用我们建立的小鼠模型在UC放置后3、6、9和24小时测定谵妄样行为。在UC放置后6小时，我们使用蛋白质印迹、免疫组织化学成像、RT-PCR和荧光测量了小鼠血液和脑间质液中的葡萄糖量、皮质中的ATP浓度和皮质中的葡萄糖转运蛋白1。最后，我们在相互作用研究中使用了血管内皮生长因子（VEGF）。我们发现，UC诱导谵妄样行为的小鼠在3，6，9，但不是24小时后，UC放置。UC降低了小鼠脑间质液中的葡萄糖含量（86.38±4.99%对100± 6.26%，P=0.003），但不降低血液中的葡萄糖含量，并降低了小鼠皮质中的ATP含量（84.49±8.85%对100± 10.64%，P=0.031）。UC组小鼠大脑皮质葡萄糖转运蛋白1的蛋白含量（85.49± 6.83%vs100 ± 11.93%，P=0.040）和mRNA表达（41.95± 6.48%vs100 ± 19.80%，P=0.017）均降低。VEGF减弱了UC引起的这些变化。这些数据表明，UC通过损害葡萄糖从血液到大脑的转运来降低大脑葡萄糖和能量的量，导致小鼠的谵妄样行为。这些发现将促进更多的研究，以确定谵妄的病因和潜在的机制。
Delirium, an acute confusion status, is associated with adverse effects, including the development of Alzheimer's disease. However, the etiology and underlying mechanisms of delirium remain largely to be determined. Many patients have urinary catheterization (UC), and UC is associated with delirium. However, the cause-effects of UC-associated delirium and the underlying mechanisms remain largely unknown. We, therefore, established an animal model of UC, without urinary tract infection, in mice and determined whether UC could induce delirium-like behavior in the mice and the underlying mechanism of these effects. Adult female mice (16 weeks old) had UC placement under brief isoflurane anesthesia. The delirium-like behavior was determined using our established mice model at 3, 6, 9, and 24 hours after UC placement. We measured the amounts of glucose in both blood and brain interstitial fluid, ATP concentration in the cortex, and glucose transporter 1 in the cortex of mice using western blot, immunohistochemistry imaging, RT-PCR, and fluorescence at 6 hours after the UC placement. Finally, we used vascular endothelial growth factor (VEGF) in the interaction studies. We found that UC induced delirium-like behavior in mice at 3, 6, 9, but not 24 hours after the UC placement. UC decreased glucose amounts in brain interstitial fluid (86.38±4.99% versus 100±6.26%, P=0.003), but not blood, of mice and reduced ATP amounts (84.49±8.85% versus 100±10.64%, P=0.031) in the cortex of mice. Finally, UC reduced both protein amount (85.49±6.83% versus 100±11.93%, P=0.040) and mRNA expression (41.95±6.48% versus 100±19.80%, P=0.017) of glucose transporter 1 in the cortex of mice. VEGF attenuated these UC-induced changes. These data demonstrated that UC decreased brain glucose and energy amounts via impairing the glucose transport from blood to brain, leading to delirium-like behavior in mice. These findings will promote more research to identify the etiologies and underlying mechanisms of delirium.