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

Figure 1

The sources of ROS in ICH: the MPTP can be opened by ROS and Ca²⁺, followed by ROS release. NMDA receptor activation by glutamate causes cellular Ca²⁺ overload, whereas APMA receptors also contribute to Ca²⁺ overload in the mitochondria. Ferrous iron can be transported into the cell through DMF1 and consequently loaded into the mitochondria by ABC-7; hemin binds with hemopexin and is transported into the cell through LRP1; then, inside the cell, hemin is catalysed by HO-1 into ferrous iron, which is then transported into the mitochondria; ferrous iron is used in the reaction to transform H₂O₂ into the hydroxyl radical, which is a very active radical in oxidative damage. In addition, ROS can also be produced by NOX (ROS: reactive oxygen species; Fe²⁺: ferrous iron; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor; : superoxide radical; ^•OH: hydroxyl radical; IRP-2: iron regulatory protein-2; NMDA: N-methyl-D-aspartic acid receptor; fer-1: ferrostatin-1; DMT1: divalent metal transporter 1; HO-1: hemoxygenase-1; MPTP: mitochondrial permeability transition pore; NADPH: adenine dinucleotide phosphate; NOX: adenine dinucleotide phosphate oxidase).