Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study
Vasunilashorn SM., Ngo LH., Dillon ST., Fong TG., Carlyle BC., Kivisäkk P., Trombetta BA., Vlassakov KV., Kunze LJ., Arnold SE., Xie Z., Inouye SK., Libermann TA., Marcantonio ER., Dickerson B., Fong T., Jones R., Travison T., Hooker J., Hshieh T., Ngo L., Otu H., Racine A., Schmitt EM., Touroutoglou A., Abdeen A., Ayres D., Earp B., Lange J., Brick G., Chen A., Davis R., Drew J., Iorio R., Kornack F., Weaver M., Webber A., Wilk R., Shaff D., Armstrong B., Banda A., Bertrand S., D’Aquila M., Gallagher J., Hightower B., Malloy S., Nee J., Nobuhara C., Overstreet A., Urick D., Xu G., Arabasz G., Brickhouse M., Butterfield R., Hsu S., Makaretz S., Sore J., Chen F., Gou Y., Tommet D., Carretie S., Gruen T., Tasker K.
Background: Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods: We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results: Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p