Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

Figure 2

The sources of oxidative stress and the cell death pathways induced by oxidative stress following intracerebral hemorrhage. Oxidative stress after ICH is a consequence of prooxidant overproduction as well as deactivation of antioxidases such as SOD. The Hb-heme-iron metabolic axis due to erythrocyte lysis represents the major sources of ROS. Neuroinflammation evoked by ICH involves the activation of microglia and the infiltration of leukocyte which is another important contributor to the production of ROS. Activation of prooxidases including NOS and NOX during ICH also releases plenty of free radicals. Other factors which can generate ROS include mitochondria dysfunction. Oxidative stress causes cell death by direct oxidation of lipid, protein, and DNA or via induction of neuronal death mediated by PKC/CK2, ERK, NF-κB, JNK signaling pathways as well as cytochrome c release, and MMP-9 activation. PKC: protein kinase C; ERK: extracellular signal-regulated kinase; NF-κB: nuclear factor kappa B; JNK: c-Jun N-terminal kinase; ROS: reactive oxygen species; RNS: reactive nitrogen species; NOS: nitric oxide synthase; NOX: nicotinamide adenine dinucleotide phosphate oxidase; MMP-9: matrix metalloproteinases-9.