Neuroinflammation in Delirium: A Postmortem Case-Control Study
Neuroinflammation in Delirium: A Postmortem Case-Control Study
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DOI：
10.1089/rej.2011.1185
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发表时间：
2011-12-01
影响因子：
2.6
通讯作者：
de Rooij, Sophia E. J. A.
中科院分区：
文献类型：
--
作者：
van Munster, Barbara C.;Aronica, Eleonora;de Rooij, Sophia E. J. A.
背景：谵妄可以被假设为患有神经退行性疾病的老年人疾病行为的极端表现。本研究的目的是探讨是否增加脑炎症与小胶质细胞，星形胶质细胞，细胞因子活化存在于谵妄患者相比，nondelirious patients.Methods：尸检脑组织9例谵妄进行了比较，6个年龄匹配的对照无谵妄。人类白细胞抗原-DR（HLA-DR）和CD 68细胞计数和胶质细胞酸性蛋白（GFAP）、白细胞介素-1 β在海马、额叶皮质和白色物质中测定IL-1 β、IL-6、β-淀粉样蛋白和tau蛋白的免疫反应性。在73岁和70.5岁之间，谵妄患者与对照组相比没有显著差异（p = 0.72）或痴呆（22%对0%，p = 0.22）。小胶质细胞活性的两种标志物在谵妄脑标本中显示出在总脑评分（HLA-DR 129对20和CD 68 30对8.5）以及在各个脑区域中分别比对照显著更高的评分。在谵妄患者的总脑评分中，星形胶质细胞活性（GFAP）的免疫反应性更高（5.2 vs. 4.0，p = 0.05），但在各个脑区，这仅在齿状回中显著。谵妄患者的所有脑区IL-6免疫反应性均较高，而IL-1 β检测不到。共存的感染性疾病或痴呆症并没有影响整体results.Conclusions：这些初步研究结果表明，人类大脑活动的小胶质细胞，星形胶质细胞和IL-6和谵妄在老年患者之间的关联，并增加了越来越多的证据表明，炎症机制参与谵妄。
Background: Delirium can be hypothesized to be an extreme manifestation of sickness behavior in elderly persons with neurodegenerative disease. The purpose of this study was to investigate whether increased cerebral inflammation with microglial, astrocyte, and cytokine activation exists in patients with delirium compared to nondelirious patients.Methods: Postmortem brain tissue from 9 cases with delirium was compared to 6 age-matched controls without delirium. Human leukocyte antigen-DR (HLA-DR) and CD68 cell count and glial fibrillary acidic protein (GFAP), interleukin-1 beta (IL-1 beta), IL-6,beta-amyloid, and tau protein immunoreactivity were determined in hippocampus, frontal cortex, and white matter.Results: There were no significant differences in the patients with delirium compared to the controls with respect to age 73 versus 70.5 years (p = 0.72) or dementia (22% versus 0%, p = 0.22). Both markers for microglial activity showed significantly higher scores in delirium brain specimens than controls in the total brain score (HLA-DR 129 vs. 20 and CD68 30 vs. 8.5) as well as in the various brain areas separately. The immunoreactivity of astrocyte activity (GFAP) was higher in the total brain score in patients with delirium (5.2 vs. 4.0, p = 0.05), but in the various brain areas this was only significant in the dentate gyrus. IL-6 immunoreactivity was higher in patients with delirium in all brain areas and IL-1 beta was not detectable. Coexisting infectious disease or dementia did not influence the overall results.Conclusions: These preliminary study results show an association between human brain activity of microglia, astrocytes, and IL-6 and delirium in elderly patients and add to the accumulating evidence that inflammatory mechanisms are involved in delirium.