The present findings demonstrated the involvement of the DAMP Prx1 in tPA-induced BBB dysfunction and HT after brain ischemia, which were significantly ameliorated by CD21 through the upregulation of MSR1-promoted DAMP (Prx1) clearance and inhibition of TLR4/NF-κB in tMCAO mice and cultured primary microglial cells. Here, PLAT is linked to brain ischemia.