Oxidant mechanisms in neonatal hypoxia-ischemia

The neonatal brain appears to be selectively vulnerable to oxidative stress . Several potential mechanisms associated with altered reactive oxygen spec ies metabolism would explain the increased susceptibility. They include inc reased accumulation of hydrogen peroxide with subsequent neurotoxicity. Thi s enhanced neurotoxicity from H2O2 accumulation may be related to inadequat e scavenging abilities of the immature nervous system, such as lower glutat hione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glut athione stores. The immature nervous system is rich in iron, and has more f ree iron than the mature nervous system. As H2O2 accumulates because of the se improper defense mechanisms, it is exposed to this free iron. This expos ure results in the generation of OH radical (Fenton reaction), a more poten t free radical that can cause severe damage. The rapid conversion of H2O2 t o OH in the setting of free iron sets up the immature nervous system for in creased cytotoxicity. Understanding the molecular mechanisms of oxidative s tress will lead to better therapies for neonatal hypoxia-ischemia. Copyrigh t (C) 2001 S. Karger AG, Basel.