Model by which ICH occurs in stroke after tPA infusion therapy. Introduction of therapeutic concentrations of tPA results in upregulation of LRP-1 and PAD4 by neutrophils, which results in induction of NETosis. Neutrophil-derived DNA results in activation of the cGAS-STING/TNKB1/IRF3 pathway, which promotes the release of type I interferon and IL-6 that cause BBB leak.