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

Cerebral ischemia-reperfusion injury is a severe neurovascular disease that urgently requires effective therapeutic interventions. Recently, hydrogen sulfide (HS) has garnered significant attention as a potential treatment for stroke; however, the precise and targeted delivery of HS remains a considerable challenge for its clinical application. We have developed HSDF-NH, a novel HS donor characterized by high selectivity, self-reporting capabilities, and the ability to penetrate the blood-brain barrier (BBB). HSDF-NH effectively scavenges reactive oxygen species (ROS) while generating HS, with emitted fluorescence facilitating the visualization and quantification of HS 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). As a ROS-responsive, self-reporting, and fluorescent HS donor, HSDF-NH holds considerable promise for the treatment of ischemic diseases beyond stroke.