Stroke Recovery Dominated by Dysregulation of Complement System – A Longitudinal Proteomics Pathway Analysis

Post-stroke recovery is an ongoing process as the brain attempts to reverse or minimize ischemia- induced disturbances in multiple biological systems. Currently, the longitudinal profile of molecular changes in patients post-stroke is relatively unknown. We therefore aimed to characterise biological pathways in plasma involved in post-stroke recovery using a discovery proteomics workflow coupled with a topological pathway systems biology approach. Blood samples (n = 180, EDTA plasma) were taken from a subgroup of 60 first episode stroke survivors from the Australian START cohort over 3 timepoints: 3-7 days (T1), 3-months (T2) and 12-months (T3) post primary event . Samples were analysed by liquid chromatography mass spectrometry (LC-MS) on the Q Exactive HF hybrid quadrupole-Orbitrap (Thermo-Fisher Scientific) using label-free quantification. The proteomics results were analysed for differential expression of all identified proteins for all available pairwise time-point comparisons. The resulting significant lists of proteins were then submitted for Gene Graph Enrichment Analysis (GGEA).