Oxidative damage and repair in the developing nervous system

Excessive production of reactive oxygen species (ROS) is a recognized cause of cell injury. In contrast to such well recognized cell injury, oxidative stress plays a role in cell proliferation, differentiation and tumor promotion. This review examines the role of oxidative stress in initiating and promoting the establishment of normal or abnormal neuronal patterns and subsequent neurogenesis within the central and peripheral nervous system. In particular, the role of apoptosis in both normal and abnormal neuronal development and maturation will be examined with special reference to the induction of apoptotic cell death following abusive ligand-induced ion movements. The interaction of oxidant stress and immediate-early response gene activation is discussed with further reference to the induction of apoptosis. While glutamate receptor activation appears mandatory for coordinate maturation and neuritogenesis, such neuronal survival and differentiation is intimately dependent upon the intracellular glutathione redox potential, maintained by cystine uptake. Selected examples of reactive oxygen species induced injury pertaining to developmental neurotoxicology are presented and include starvation, irradiation injury and glutamate excitotoxicity.