Research Progress of Blood-Based Biomarkers for the Diagnosis and Prognostic Evaluation of Acute Ischemic Stroke

Blood-based biomarkers offer a promising “biochemical imaging” approach for acute ischemic stroke (AIS) management, providing objective and accessible tools to complement conventional neuroimaging. This narrative review synthesizes recent advances in biomarkers derived from multiple neurovascular unit (NVU) compartments, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neuron-specific enolase (NSE), neurofilament light chain (NfL), matrix metalloproteinase-9 (MMP-9), Claudin-5, Occludin, brain-derived neurotrophic factor (BDNF), interleukin-33 (IL-33), tumor necrosis factor-alpha (TNF-alpha), PARK7/DJ-1, glycogen phosphorylase BB (GP-BB), and circulating microRNAs. We focus on their stage-specific clinical utility across three scenarios: (1) ultra-early differentiation between ischemic stroke and intracerebral hemorrhage in prehospital and emergency settings; (2) dynamic prediction and monitoring of hemorrhagic transformation after reperfusion therapies; and (3) assessment of infarct burden, neurorepair potential, and long-term functional outcomes. Despite their promise, clinical translation remains hindered by assay platform heterogeneity, lack of standardized cut-off values, limited cost-effectiveness data, and insufficient prospective validation adjusted for key covariates such as age and renal function. We further discuss multi-marker panel construction, including strategies to address biomarker collinearity and overfitting. Future directions emphasize stage-specific panels, point-of-care testing devices, and artificial intelligence algorithms to advance precision medicine in stroke care.