Biomarkers in Plasma Exosomes Reveal Molecular Pathways of Postoperative Delirium: New Horizons from Diagnosis to Treatment

ABSTRACT: Background: Delirium diagnosis currently lacks objective biomarkers and is based solely on clinical observation, with incomplete understanding of underlying mechanisms. This study aims to explore the proteomic and metabolomic profiles of exosomes for postoperative delirium (POD) diagnosis and to understand the associated pathophysiological frameworks. Methods: We conducted integrated analyses of proteomics and metabolomics on plasma-derived exosomes from both non-POD controls and POD patients. The study utilized Connectivity Map (CMap) methodology to identify potential small-molecule drugs and performed molecular docking assessments to explore binding affinities with the MMP9 enzyme. Results: Significant differences in exosomal metabolites and proteins between POD patients and controls were identified, emphasizing pathways related to neuroinflammation and blood-brain barrier integrity. Our CMap analysis led to the identification of promising therapeutics, with molecular docking revealing high-affinity MMP9 inhibitors, suggesting new therapeutic avenues for POD. Conclusions: This research highlights MMP9, TLR2, ICAM1, S100B, and glutamate as key biomarkers in POD pathophysiology and underscores the importance of neuroinflammation and blood-brain barrier roles. The findings suggest targeted therapeutic strategies, reinforcing the necessity of multidimensional biomarker analysis in POD intervention, and providing insights into potential new treatment options.

ORGANISM(S): Homo Sapiens

SUBMITTER: Feng Qu  

PROVIDER: PXD051005 | iProX | Wed Mar 27 00:00:00 GMT 2024

REPOSITORIES: iProX