Recent advances in reaction-based fluorescent probes for the detection of central nervous system-related pathologies in vivo

•Recent progress on reaction-based fluorescent probes for biomolecules in brain.•Focusing on central nervous system diseases-related biomarkers.•Design principles for specific analytes and the challenges were discussed. Central nervous system (CNS)-related pathologies have been historically recognized as one of the hotspots in medical research. Extensive evidences have shown that biomolecules including small molecules and enzymes are tightly linked to diverse of disorders in human brain. To decipher the pathological roles of these molecules in closely linked mental illness, it is of great significance to develop effective approaches for imaging the associated biomarkers in CNS. Owning to its unique advantages, such as non-invasiveness and real-time imaging, fluorescence imaging (FI) has been developed as a robust tool for tracking various molecules in brain. Notably, an increasing number of fluorescent probes have been proposed to track the molecules in brain in vivo over the past decades. In this review, we systematically summarized the methods for the designs and applications of reaction-based fluorescent probes according to the intrinsic characteristic of biomarkers in CNS. Furthermore, the potential challenges for monitoring biomolecules and the suggestions for developing new reaction-based fluorescent probes in this field were also discussed. We hope that the information herein can help break the dilemmas such as the sensitivity requirement and limited bioapplications.