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0 reviewsSUMMARYPatients with an ischemic stroke are often predisposed to emotional disorders. However, the mechanismsunderlying post-stroke emotional disorders (PSEDs) remain unclear. Recent research highlights the role ofneuroinflammation, driven primarily by infiltration of circulating immune cells within the brain parenchymaand accompanied by blood-brain barrier (BBB) disruption, in secondary emotional disorders. Combining human cohort and animal model data, we identified serum neutrophil extracellular traps (NETs) as significantcontributors to PSEDs. Conditional knockout strategies and -omics analyses convergently identified centralNETs as the specific modulator of PSEDs. We further elucidated that astrogliosis is catalyzed by lipocalin 2(Lcn2) released from NETs, which constituted the core mechanism underlying PSEDs. Additionally, we provided proof-of-concept evidence that transcranial direct current stimulation (tDCS) can suppress Lcn2release and alleviate PSEDs. Collectively, these findings delineated a distinct peripheral-central neuroimmune interaction pattern following BBB damage and highlighted the potential of non-invasive stimulationin effectively reshaping the neuroimmune environment.
