Advances in small-molecule fluorescent probe development for bioimaging of ischemic stroke-associated biomarkers

Ischemic stroke initiates with the interruption of cerebral blood flow, and reperfusion following revascularization may subsequently trigger cerebral ischemia-reperfusion injury. This secondary injury is characterized by dynamic molecular changes, including redox imbalance, mitochondrial dysfunction, blood-brain barrier (BBB) disruption, neuroinflammation, regulated cell death, microenvironmental remodeling, and ion homeostasis disturbance. Conventional neuroimaging is indispensable for anatomical and perfusion assessment, but it is less applicable to the real-time visualization of transient molecular events. Small-molecule fluorescent probes provide high sensitivity, tunable structures, and high spatiotemporal resolution, making them useful chemical tools for bioimaging stroke-associated biomarkers in situ. This review reorganizes recent fluorescent probes according to the pathological cascade of ischemic stroke, with a focus on reactive oxygen species, sulfur-containing redox species, pathological microenvironmental parameters, protein- and structure-related biomarkers, and ionic biomarkers. We further discuss their design strategies, response mechanisms, optical readouts, subcellular targeting, BBB permeability, model compatibility, and intervention-based validation. Future research should prioritize brain accessibility, quantitative reliability, biosafety, and mechanistic validation, so as to better correlate fluorescence signals with well-defined pathological processes.