Proteomic Signatures of Ischemic and Hemorrhagic Stroke: A PRIDE-Based Narrative Review toward Candidate Molecular Stratification

This PRIDE-based narrative paper synthesizes existing proteomic studies of ischemic and hemorrhagic stroke to identify recurrent molecular signatures and discuss their translational relevance. Current acute stroke workflows rely primarily on neuroimaging to distinguish ischemic from hemorrhagic stroke, yet circulating protein signatures may provide complementary biological information on vascular injury, blood–brain barrier disruption, thromboinflammation, and central nervous system damage. The paper was deliberately restricted to PRIDE-deposited mass spectrometry proteomics data sets to enable data set-level interrogation, harmonization of reported protein identities, and comparison of recurrent molecular signatures across publicly available studies. Across the reviewed studies, four recurrent biomarker families emerged: acute-phase/coagulation proteins, blood–brain barrier and matrix-remodeling proteins, lipoprotein-related metabolic modifiers, and central nervous system injury markers. Key proteins such as glial fibrillary acidic protein (GFAP), matrix metalloproteinase-9 (MMP-9), apolipoprotein C–I (ApoC-I), ubiquitin C-terminal hydrolase L1 (UCH-L1), von Willebrand factor (vWF), and C-reactive protein (CRP) appear to define candidate molecular axes related to injury–thrombosis and permeability–repair biology. Ischemic and hemorrhagic stroke share a conserved inflammatory–coagulatory response but differ in central nervous system injury and vascular permeability signals, supporting further evaluation of compact multiprotein panels as candidate tools for subtype stratification and prognosis. By reviewing existing PRIDE-based proteomic evidence, this article highlights candidate biomarkers and biological pathways that may inform future studies of stroke subtype stratification, hemorrhagic risk assessment, and trial enrichment. However, current evidence remains insufficient for clinical implementation. Larger prospective multicenter studies, standardized sampling protocols, and targeted assay validation are required before proteomic biomarker panels can be considered for acute stroke decision support.