Diagnostic biomarkers of ischemic stroke: strengths and limitations across blood, urine, and saliva.

Ischemic stroke is a major cause of death and long-term disability worldwide. It requires quick medical intervention within a short timeframe to save brain tissue. While neuroimaging is the preferred method for diagnosis, it is often unavailable in prehospital and low-resource settings. This gap has led to a strong interest in finding biological markers that can quickly confirm ischemia and help differentiate it from hemorrhagic strokes and stroke mimics. This review summarizes the frequently studied diagnostic biomarkers found in blood, urine, and saliva, organizing them by molecular pathways such as neuronal injury, inflammation, hemostasis, and oxidative stress. Blood-based markers are currently the most advanced, with brain-specific proteins such as glial fibrillary acidic protein providing high specificity for early stroke subtyping. However, many other markers for neuronal injury have slow kinetics or poor specificity to differentiate stroke subtypes, which limits their immediate utility. Emerging research shows that brain-specific proteins and proteomic/metabolic signatures can be detected in urine and saliva, but these methods are still experimental and lack validation in larger acute patient groups. Overall, the current evidence indicates that no single biomarker or biofluid is sufficient for early ischemic stroke diagnosis. Future progress will likely depend on multi-marker strategies, standardized methods, and early-timepoint sampling.