γ-Glutamylcysteine ameliorates blood-brain barrier permeability and neutrophil extracellular traps formation after ischemic stroke by modulating Wnt/β-catenin signalling in mice

During the inflammatory response after stroke, the blood-brain barrier (BBB) is significantly disrupted, compromising its integrity. This disruption allows many peripheral neutrophils to infiltrate the injury site in the brain and release neutrophil extracellular traps (NETs), which further increase BBB permeability. In this study, we aimed to investigate the protective effects of gamma-Glutamylcysteine (gamma-GC), an immediate precursor of GSH, against BBB breakdown and NET formation after ischemic stroke. Our data indicated that gamma-GC treatment effectively attenuated BBB damage, decreased neutrophil infiltration, and suppressed the release of NETs, ultimately leading to the amelioration of ischemic injury. Transcriptomic data and subsequent validation studies revealed that mechanistically, gamma-GC exerts its effect by activating the Wnt/beta-catenin pathway after ischemic stroke. This research suggests that gamma-GC may hold promise as a therapeutic agent for alleviating brain injury following an ischemic stroke.