Kim Annink

11 General introduction with oxygen is converted by xanthine-oxidase into superoxide and uric acid. Superoxide itself is toxic for the brain, but is also responsible for the activation of other destructive pathways that lead to brain injury: superoxide interacts with nitric oxide (NO) leading to the formation of the toxic peroxynitrite and to conversion of non-protein bound iron into hydroxyl free radicals, which is the most toxic free radical in nature (9–12). This early production of free radicals (already starting within the first minutes up to the first hours of life) eventually leads to inflammation, apoptotic activity and inhibition of trophic factors. This impairs repair and neo- neurogenesis (5,13,14). (Figure 1) The pattern of brain injury might differ depending on the timing and length of the hypoxic event. The majority of infants with HIE suffer from an acute sentinel event leading to injury of the most highly demanding metabolic areas in the brain, such as the deep grey matter including the basal ganglia and thalami (15). Injury of the deep grey matter is more likely to result in motor problems on the long-term (16). Infants with HIE who suffered from subacute-to-chronic asphyxia more often develop watershed injury of the white matter (15) because the borderline areas of the major supplying cerebral arteries (anterior-, middle- and posterior arteries) are especially vulnerable for changes in blood flow. The outcome of infants with only watershed type injury is often better than of infants with deep grey matter type injury. Watershed type injury is more likely to result in cognitive and behavioral problems than in motor problems (15,17). A mixture of both patterns is also possible. In the most severe cases of perinatal asphyxia this can result in near-total brain injury (15). 1