Systemic infection is associated with long-term cognitive deficits and functional decline. In this study we hypothesized that severe systemic inflammation leads to a neuroinflammatory response that is characterized by microglial activation, and that these effects might be more pronounced in patients using medication with anticholinergic side-effects. Based on the results of a pilot study in 8 patients, we assessed the number of MHC-II and CD-68 positive cells by immunohistochemistry and compared the number of microglia in specific brain regions of 16 well-characterized patients with septic shock and 15 controls. In the pilot study, patients with sepsis tended to have higher density of MHC-II and CD-68 positive microglia in the basal ganglia (putamen, caudate nucleus and globus pallidus) and of MHC-II positive microglia in the hippocampus. In the validation study, patients with sepsis had a significantly higher number of CD-68 positive cells in hippocampus (1.5 fold; p = 0.012), putamen (2.2 fold; p = 0.008) and cerebellum (2.5 fold; p = 0.011) than control patients. The density of MHC-II positive microglia was similar between sepsis and control groups. There was no consistent correlation between microglia counts and anti-cholinergic activity drugs score. In patients who die during septic shock, severe systemic inflammation is accompanied by localized and strong upregulation of CD-68 positive microglia, but not of MHC-II positive microglia. We identified regional differences in the brain with increased microglial activation in putamen, hippocampus and cerebellum.

中文翻译：

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全身感染和小胶质细胞激活：脓毒症患者的前瞻性尸检研究


全身感染与长期认知缺陷和功能衰退有关。在这项研究中，我们假设严重的全身炎症会导致以小胶质细胞激活为特征的神经炎症反应，并且这些影响在使用具有抗胆碱能副作用的药物的患者中可能更为明显。根据 8 名患者的初步研究结果，我们通过免疫组织化学评估了 MHC-II 和 CD-68 阳性细胞的数量，并比较了 16 名特征明确的感染性休克患者和 15 名对照者特定大脑区域的小胶质细胞数量。在初步研究中，脓毒症患者的基底节（壳核、尾状核和苍白球）中的 MHC-II 和 CD-68 阳性小胶质细胞以及海马中的 MHC-II 阳性小胶质细胞密度往往较高。在验证研究中，脓毒症患者的海马体（1.5 倍；p = 0.012）、壳核（2.2 倍；p = 0.008）和小脑（2.5 倍；p = 0.011）中的 CD-68 阳性细胞数量显着高于正常患者。控制患者。脓毒症组和对照组之间 MHC-II 阳性小胶质细胞的密度相似。小胶质细胞计数与抗胆碱能活性药物评分之间没有一致的相关性。在感染性休克期间死亡的患者中，严重的全身炎症伴随着 CD-68 阳性小胶质细胞的局部强烈上调，但 MHC-II 阳性小胶质细胞则不然。我们发现大脑中存在区域差异，壳核、海马体和小脑的小胶质细胞激活增加。