FIGURE 3.

Overview of necroptosis pathways following ICH. Microglia are activated after ICH. They release tumor necrosis factor (TNF) to initiate necroptosis by binding to TNF receptor. Phosphorylation of receptor-interacting protein 1 (RIP1) to develop necrosome also occurs. The necrosome cooperates with receptor-interacting protein 3 (RIP3) for the recruitment of mixed lineage kinase domain-like protein (MLKL). The complex of MLKL and RIP3 transfers to the cell membrane and forms a channel to cause the inward flow of Ca²⁺ and Na⁺. Finally, the cell dies through the necroptotic pathway.