Enhanced HRG production following rt-PA treatment modulate neutrophil immune activity and hemorrhagic transformation in ischemic stroke

Intravenous thrombolysis (IVT) with recombinate tissue plasminogen activatior (rt-PA) remains the primary approach for the treatment of acute ischemic stroke (AIS). Based on the short half-life of rt-PA, it is speculated that the coagulative/fibrinolytic cascade induced by alteplase administration might have subsequent longer effect on immune modulation. The exact role of Histidine-rich glycoprotein (HRG), which was found elevated following thrombolysis in this study, on affecting the innate immunity and hemorrhagic transformation (HT) following thrombolysis was investigated in this study. RNA sequencing was performed to show different expressed genes under HRG treatment and revealing the potential regulating pathway. Overall design: To investigate the effect of HRG on human peripheral blood neutrophils,fresh blood samples were obtained from patients diagnosed with ischemic stroke.Neutrophils isolated from human peripheral blood were cultured with PBS, rt-PA, and rt-PA+HRG for 2.5 hours,then comparative gene expression profiling analysis of RNA-seq date for neutrophils under these three treatments.