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A Pathway Proteomic Profile of Ischemic Stroke Survivors Reveals Innate Immune Dysfunction in Association with Mild Symptoms of Depression - A Pilot Study

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posted on 01.11.2021, 23:00 by VA Nguyen, Leeanne CareyLeeanne Carey, Loretta Giummarra, Pierre Faou, Ira CookeIra Cooke, DW Howells, Tamara TseTamara Tse, SL Macaulay, H Ma, SM Davis, GA Donnan, Sheila CrewtherSheila Crewther
Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery-Åsberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI-MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro-inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the involvement of inflammatory and immune mechanisms in PSD symptoms and further demonstrate the value and feasibility of the proteomic approach in stroke research.


We acknowledge financial support for conduct of the research from the Commonwealth Scientific and Industrial Research Organization (CSIRO) of Australia, Flagship Collaboration Fund through the Preventative Health Flagship; data collection and project planning by the Stroke Imaging, Prevention and Treatment research team (; support for analysis and write up and/or researchers from the James S. McDonnell Foundation 21st Century Science Initiative in Cognitive Rehabilitation - Collaborative Award (# 220020413); Victorian Government's Operational Infrastructure Support Program; an Australian Research Council Future Fellowship awarded to LC (#FT0992299); and a La Trobe University Post Graduate Scholarship supported by the Understanding Diseases Research Focus Group at La Trobe University.


Publication Date



Frontiers in Neurology





Article Number



16p. (p. 1-16)


Frontiers Media



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