关键词: bacterial translocation biomarkers cytokines inflammation leaky gut neuro-immune

来  源:   DOI:10.3389/fneur.2024.1294689   PDF(Pubmed)

Abstract:
UNASSIGNED: Delirium is accompanied by immune response system activation, which may, in theory, cause a breakdown of the gut barrier and blood-brain barrier (BBB). Some results suggest that the BBB is compromised in delirium, but there is no data regarding the gut barrier. This study investigates whether delirium is associated with impaired BBB and gut barriers in elderly adults undergoing hip fracture surgery.
UNASSIGNED: We recruited 59 older adults and measured peak Delirium Rating Scale (DRS) scores 2-3 days after surgery, and assessed plasma IgG/IgA levels (using ELISA techniques) for zonulin, occludin, claudin-6, β-catenin, actin (indicating damage to the gut paracellular pathway), claudin-5 and S100B (reflecting BBB damage), bacterial cytolethal distending toxin (CDT), LPS-binding protein (LBP), lipopolysaccharides (LPS), Porphyromonas gingivalis, and Helicobacter pylori.
UNASSIGNED: Results from univariate analyses showed that delirium is linked to increased IgA responses to all the self-epitopes and antigens listed above, except for LPS. Part of the variance (between 45-48.3%) in the peak DRS score measured 2-3 days post-surgery was explained by independent effects of IgA directed to LPS and LBP (or bacterial CDT), baseline DRS scores, and previous mild stroke. Increased IgA reactivity to the paracellular pathway and BBB proteins and bacterial antigens is significantly associated with the activation of M1 macrophage, T helper-1, and 17 cytokine profiles.
UNASSIGNED: Heightened bacterial translocation, disruption of the tight and adherens junctions of the gut and BBB barriers, elevated CDT and LPS load in the bloodstream, and aberrations in cell-cell interactions may be risk factors for delirium.
摘要:
谵妄伴随着免疫反应系统的激活,可能,理论上,导致肠屏障和血脑屏障(BBB)的破坏。一些结果表明,BBB在谵妄中受损,但是没有关于肠道屏障的数据。这项研究调查了在接受髋部骨折手术的老年人中,谵妄是否与BBB和肠道屏障受损有关。
我们招募了59名老年人,并在手术后2-3天测量了谵妄评分(DRS)峰值,并评估血浆IgG/IgA水平(使用ELISA技术)的zonulin,occludin,claudin-6,β-catenin,肌动蛋白(表明对肠道细胞旁通路的损害),claudin-5和S100B(反映BBB损伤),细菌细胞致死膨胀毒素(CDT),LPS结合蛋白(LBP),脂多糖(LPS),牙龈卟啉单胞菌,和幽门螺杆菌。
单变量分析的结果表明,谵妄与对上述所有自身表位和抗原的IgA反应增加有关,除了LPS。手术后2-3天测量的峰值DRS评分的部分差异(45-48.3%)由针对LPS和LBP(或细菌CDT)的IgA的独立作用解释,基线DRS评分,和以前的轻度中风。IgA对细胞旁通路和BBB蛋白和细菌抗原的反应性增加与M1巨噬细胞的活化显著相关,T辅助-1和17细胞因子谱。
细菌易位加剧,肠和BBB屏障的紧密和粘附连接的破坏,血液中CDT和LPS负荷升高,细胞间相互作用的异常可能是谵妄的危险因素。
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