Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains unclear in humans, primarily owing to limitations of in vivo biomarkers of neuroinflammation which vary in sensitivity, specificity, validity, and reliability. In the present study, [¹¹C]PBR28 positron emission tomography, cerebrospinal fluid (CSF), and blood plasma biomarkers of inflammation were assessed pre-operatively and 1-month post-operatively in a cohort of patients (N = 36; 30 females; ≥70 years old) undergoing major orthopedic surgery under spinal anesthesia. Delirium incidence and severity were evaluated daily during hospitalization. Whole-brain voxel-wise and regions-of-interest analyses were performed to determine the magnitude and spatial extent of changes in [¹¹C]PBR28 uptake following surgery. Results demonstrated that, compared with pre-operative baseline, [¹¹C]PBR28 binding in the brain was globally downregulated at 1 month following major orthopedic surgery, possibly suggesting downregulation of the immune system of the brain. No significant relationship was identified between post-operative delirium and [¹¹C]PBR28 binding, possibly due to a small number (n = 6) of delirium cases in the sample. Additionally, no significant relationships were identified between [¹¹C]PBR28 binding and CSF/plasma biomarkers of inflammation. Collectively, these results contribute to the literature by demonstrating in a sizeable sample the effect of major surgery on neuroimmune activation and preliminary evidence identifying no apparent associations between [¹¹C]PBR28 binding and fluid inflammatory markers or post-operative delirium.

大手术与全身炎症级联有关，在某些情况下，可能通过神经炎症机制导致短暂和/或持续的认知能力下降。然而，人类手术、周围和中枢神经系统炎症以及术后认知结果之间的关系仍不清楚，这主要是由于体内神经炎症生物标志物的敏感性、特异性、有效性和可靠性各不相同的局限性。在本研究中，对一组患者（ N  = 36；30 名女性）进行术前和术后 1 个月的[ 11 C]PBR28 正电子发射断层扫描、脑脊液 (CSF) 和血浆炎症生物标志物进行^评估；≥70岁）在脊椎麻醉下接受大型骨科手术。住院期间每天评估谵妄的发生率和严重程度。进行全脑体素分析和感兴趣区域分析，以确定手术后[ ^{11 C]PBR28 摄取变化的幅度和空间范围。}结果表明，与术前基线相比，大型骨科手术后 1 个月，大脑中的 [ ¹¹ C]PBR28 结合全面下调，这可能表明大脑免疫系统的下调。术后谵妄与 [ ¹¹ C]PBR28 结合之间没有发现显着关系，可能是由于 样本中谵妄病例数量较少 ( n = 6)。此外，[ ¹¹ C]PBR28 结合与 CSF/血浆炎症生物标志物之间没有发现显着关系。总的来说，这些结果通过在大量样本中证明大手术对神经免疫激活的影响以及初步证据表明[ 11 ^C ]PBR28 结合与体液炎症标志物或术后谵妄之间没有明显关联，为文献做出了贡献。