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 n euronal patterns and subsequent neurogenesis within the central and pe ripheral nervous system. In particular, the role of apoptosis in both normal and abnormal neuronal development and maturation will be examin ed with especial reference to the induction of apoptotic cell death fo llowing abusive ligand-induced ion movements. The interaction of oxida nt stress and immediate-early response gene activation is discussed wi th further reference to the induction of apoptosis. While glutamate re ceptor activation appears mandatory for coordinate maturation and neur itogenesis, such neuronal survival and differentiation is intimately d ependent upon the intracellular glutathione redox potential, maintaine d by cystine uptake. Selected examples of reactive oxygen species indu ced injury pertaining to developmental neurotoxicology are presented a nd include starvation, irradiation injury and glutamate excitotoxicity . (C) 1994 Intox Press, Inc.