Kim Annink

151 Allopurinol: old drug, new indication in neonates? at birth and a second peak caused by the reoxygenation and reperfusion after birth, called reperfusion injury (21,22). Figure 1 shows the pathophysiologic processes of brain damage after perinatal asphyxia. Figure 1: Activated pathways leading to brain damage in HIE (22). (adapted from van Bel and Groenendaal, 2016) The acute moment of hypoxia during birth (which is caused by deficient oxygen supply e.g. due to placental abruption or other sentinel events) results in primary energy failure and, consequently, the degradation of adenosine triphosphate (ATP) and eventually necrotic cell death (21,22). This leads to the release of excitatory neurotransmitters as glutamate, which results in the over-activation of the N-methyl D-aspartate (NMDA) receptors and failure of the Na-K-ATPase pump (22-24). Both generate a calcium influx into the cells, leading to the activation of enzymes, such as proteases, that initiate predominantly apoptotic cell death (21,25). The acute moment of fetal hypoxia also initiates the production of pro-radicals, such as NPBI, that later on can form free radicals after reoxygenation upon birth (22,26-28). ATP degradation also increases the level of adenosine, which is converted into hypoxanthine via inosine and cumulates during fetal hypoxia (5,29). These elevated hypoxanthine 7