Mechanisms Underlying Neonatal Hypoxia Ischemia

Neonatal hypoxic ischemic encephalopathy (HIE) is a common health problem and occurs in approximately 16 in 1000 term infants every year. After the initial hypoxic ischemic insult, brain injury evolves for days and possibly even weeks. The severity of the injury depends on the gestational age and duration of the insult. The exact underlying mechanisms of neonatal HIE remain undefined and many differences exist between adult and neonatal brain injury. In order to better understand the mechanisms underlying hypoxic ischemic injury and develop more effective therapies for HIE, different animal models of neonatal brain injury was developed. The proposed mechanisms include excitotoxicity, necrotic and apoptotic neurodegeneration, oxidative stress, inflammation and non-NMDA dependent pathways. New evidence suggests that non-NMDA-dependent pathways, such as the Na + /H + exchangers and non-selective Ca 2+ -activated ATP-sensitive cation channels, may also be involved in HIE. Activation of these mechanisms after the hypoxic and ischemic insult contributes to pathogenesis simultaneously or sequentially. This review summarizes the different models of neonatal HIE, major cellular and molecular mechanisms, potential therapies that are currently investigated either in preclinical experimental animal models or in clinical trials in hypoxic ischemic brain injury in neonates.