Figure 10.

Model illustrating hemorrhage/hemin-induced genome instability, resulting interaction between senescence and ferroptosis, and a mechanism-driven combinatorial antioxidant plus chelator therapy for ICH. Hemin rapidly induces lethal DSBs in addition to ROS injury, which activate neuronal senescence. Prevention of oxidative injury by antioxidants then sensitizes cells to iron toxicity and ferroptosis. A nanoparticle of the iron chelator deferoxamine (DEF) and antioxidant PEG-HCC effectively prevents genome damage, senescence, and ferroptosis, thus mitigating ICH-induced neuronal toxicity in preclinical models.