A fluorogenic ROS-triggered hydrogen sulfide donor for alleviating cerebral ischemia-reperfusion injury

Rationale: Cerebral ischemia-reperfusion injury is a severe neurovascular disease that urgently requires effective therapeutic interventions. Recently, hydrogen sulfide (H₂S) has garnered significant attention as a potential treatment for stroke; however, the precise and targeted delivery of H₂S remains a considerable challenge for its clinical application. Methods: We have developed HSDF-NH₂, a novel H₂S donor characterized by high selectivity, self-reporting capabilities, and the ability to penetrate the blood-brain barrier (BBB). Results: HSDF-NH₂ effectively scavenges reactive oxygen species (ROS) while generating H₂S, with emitted fluorescence facilitating the visualization and quantification of H₂S release. This compound has demonstrated protective effects against cerebral ischemia-reperfusion (I/R) injury and contributes to the reconstruction of brain structure and function in a rat stroke model (tMCAO/R). Conclusion: As a ROS-responsive, self-reporting, and fluorescent H₂S donor, HSDF-NH₂ holds considerable promise for the treatment of ischemic diseases beyond stroke.