The Injury and Therapy of Reactive Oxygen Species in Intracerebral Hemorrhage Looking at Mitochondria

Figure 2

Many additional reactive oxidative species are produced after ICH. They can cause cell death and BBB disruption in the form of lipid peroxidation, DNA damage, and protein peroxidation, which contribute to the opening of the MPTP and to injury of the outer mitochondrial membrane. Once the MPTP opens, many molecules will enter into the mitochondria, and the ΔΨ will decrease, injuring the mitochondrial respiratory chain and causing ATP depletion, causing mitochondrial swelling and necrosis. In addition, ROS can injure the outer mitochondrial membrane, causing cytochrome c release and activating caspase-dependent apoptosis. Excessive ROS can also cause glutathione depletion, leading to necroptosis. Ferroptosis, characterized by iron-dependent accumulation of ROS, may be a potential apoptotic mechanism during ICH. ROS also can upregulate the expression of MMP-9, degrading tight junction proteins and the basal laminar proteins, leading to BBB disruption (ICH: intracerebral hemorrhage; ROS: reactive oxygen species; BBB: blood-brain barrier; MPTP: mitochondrial permeability transition pore; ΔΨ: transmembrane potential; MMP-9: matrix metallopeptidase 9).