Fig. 8: NINJ1-mediated plasma membrane rupture of pyroptotic endothelial cells exacerbates blood-brain barrier destruction caused by neutrophil extracellular traps in traumatic brain injury.

NETs induced by TBI interact with the TLR4 of bECs and then activate NF-κB to transfer into the nucleus, which promotes NLRP3 inflammasome formation. Then, activated caspase-1 from the NLRP3 inflammasome cleaved GSDMD and released GSDMD-N, perforating the GSDMD pores and increasing the BBB permeability. Furthermore, GSDMD pores activate NINJ1 oligomerization on the cell membrane, which mediates PMR. HMGB1 promotes neutrophil formation in NETs.