Figure 3.

Schematic diagram of production of mitochondrial ROS after ICH. Ionotropic glutamate receptors, such as NMDA receptor and APMA receptor, are activated by glutamate, causing cellular Ca²⁺ overload in cells and mitochondria, respectively. Insults, such as ROS and pressure can induce cellular Ca²⁺ overload directly through TRP channels. Ferrous iron can be transported into cells by DMT1 and then loaded into mitochondria by ABCB6. Ferrous is used to convert H₂O₂ to hydroxyl radicals, which are the active radicals causing severe oxidative damage. mPTPs are activated by Ca²⁺ and ROS to open, and ROS are subsequently released. In addition, NOX can produce ROS. ROS, reactive oxygen species; Fe²⁺, ferrous iron; AMPA, amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor; NMDA, N-methyl-D-aspartic acid receptor; fer-1, ferrostatin-1; DMT1, divalent metal transporter 1; mPTP, mitochondrial permeability transition pore; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, nicotinamide adenine dinucleotide phosphate oxidase.