• Souren Mkrtchian, Maria Eldh, Anette Ebberyd, Susanne Gabrielsson, Ákos Végvári, Sven-Erik Ricksten, Mattias Danielson, Jonatan Oras, Andreas Wiklund, Lars I Eriksson, and Marta Gómez-Galán.
• Department of Physiology and Pharmacology, Section for Anaesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.
• Br J Anaesth. 2024 Oct 18.

BackgroundPostoperative neurocognitive decline is a frequent complication triggered by unclear signalling mechanisms. This observational case-control study investigated the effects of hip or knee replacement surgery on the composition of circulating extracellular vesicles (EVs), potential periphery-to-brain messengers, and their association with neurocognitive outcomes.MethodsWe mapped the microRNAome and proteome of plasma-derived EVs from 12 patients (six with good and six with poor neurocognitive outcomes at 3 months after surgery) at preoperative and postoperative timepoints (4, 8, 24, and 48 h). Complement C3-EV association was confirmed by flow cytometry in plasma- and cerebrospinal fluid (CSF)-derived EVs, with total plasma and CSF C3 and C3a concentrations determined using enzyme-linked immunosorbent assay.ResultsDifferential expression analysis found eight dysregulated EV microRNAs (miRNAs) exclusively in the poor neurocognitive outcomes group. Pathway analysis suggested potential downregulation of proliferative pathways and activation of extracellular matrix and inflammatory response pathways in EV target tissues. Proteome analysis revealed a time-dependent increase in immune-related EV proteins, including complement system proteins, notably EV surface-associated C3. Such upward kinetics was detected earlier in the poor neurocognitive outcomes group. Interestingly, CSF-derived EVs from the same group showed a drastic drop of C3 at 48 h with unchanged concentrations in the good neurocognitive outcomes group. Functionally, the complement system was activated in both patient groups in plasma, but only in the poor neurocognitive outcomes group in CSF.ConclusionsOur findings highlight the impact of surgery on plasma- and CSF-derived EVs, particularly in patients with poor neurocognitive outcomes, indicating a potential role for EVs. The small sample size necessitates verification with a larger patient cohort.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

5 keywords...

hide…