Red blood cell involvement in fetal/neonatal hypoxia.

Free radical release plays an important role in the development of brain injury following hypoxic-ischemic encephalopathy. It causes endothelial cell damage and anomalies in NMDA receptors, synaptosome structure and astrocyte function. Mitochondrial dysfunctions caused by asphyxia, reperfusion after ischemia, arachidonic acid cascade, catecholamine metabolism and phagocyte activation are known sources of reactive oxygen species, particularly the superoxide anion (O2(-)). O2(-) mainly induces peroxidation by the Fenton/Haber Weiss reaction or via iron-oxygen complexes. Since both reactions require reactive heavy metals, non-protein-bound iron (NPBI) is essential for the induction of lipid peroxidation. Experimental studies have demonstrated the neurotoxicity of iron in ischemia-reperfusion. Normal axonal transport of brain iron is also reported to be disrupted in hypoxia-ischemia, leading to a buildup of iron in the white matter. The free iron content of erythrocytes (ICRBC) is considered a marker of oxidative stress. Free iron release is accompanied by the oxidation of membrane proteins and the appearance of senescent antigen, as measured by autologous IgG binding. Our preliminary results suggest a significant positive correlation between plasma free iron and the number of nucleated red cells in cord blood, currently considered a reliable index of lasting intrauterine asphyxia but also possessing a high predictive value for poor neurodevelopmental outcome. The rate of erythropoiesis and the entity of ICRBC are related to the degree of asphyxia and the probability of neurological impairment. Since even an increase in NPBI during asphyxia is related to a poor outcome, iron released by red cells could possibly also contribute to NPBI levels.