Stroke is a medical emergency resulting from the sudden disruption of blood flow to the brain. Managing acute stroke is challenging and requires neuroimaging to differentiate stroke subtypes and exclude other diseases mimicking stroke symptoms. Delay in initiating treatment contributes to increased mortality and disability rates. Incorporating blood biomarkers in the early triage of stroke patients might accelerate the administration of therapies. Additionally, a deeper understanding of stroke pathophysiology could improve care management, with extracellular vesicles (EVs) offering insights into molecular mechanisms involved in acute stroke through their protein cargo.

The first aim of this thesis was to explore the protein cargo of plasma-derived EVs to understand pathophysiological processes associated with acute stroke subtypes. Proteome modulations related to coagulation and inflammation were observed and distinguished hemorrhagic, LVO and non LVO ischemic stroke patients from healthy individuals. These findings suggested that plasma-derived EVs and their protein cargo may mediate important processes in acute stroke pathology.

The second aim of this thesis was to assess the diagnostic accuracy of four promising blood biomarkers in differentiating hemorrhagic and LVO strokes in a cohort of patients with acute suspected stroke recruited on board mobile stroke units. The combination of two panels, GFAP and mean arterial pressure, and D-dimer and NTproBNP, identified one third of patients with the two most severe stroke subtypes, independently of any clinical score, and could provide useful tools for prehospital triage.

Overall, these findings hold promises for improvement of acute stroke care management and patient outcomes.