Mechanisms Underlying Neonatal Hypoxia Ischemia

摘要

Neonatal hypoxic ischemic encephalopathy (HIE) is a common health problem and occurs in approximately 1-6 in 1000 term infants every year. After the initial hypoxic ischemic insult, brain injury evolves for days and possiblyeven weeks. The severity of the injury depends on the gestational age and duration of the insult. The exact underlyingmechanisms of neonatal HIE remain undefined and many differences exist between adult and neonatal brain injury. Inorder to better understand the mechanisms underlying hypoxic ischemic injury and develop more effective therapies forHIE, 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. Newevidence suggests that non-NMDA-dependent pathways, such as the Na+ /H+ exchangers and non-selective Ca2+-activatedATP-sensitive cation channels, may also be involved in HIE. Activation of these mechanisms after the hypoxic andischemic insult contributes to pathogenesis simultaneously or sequentially. This review summarizes the different modelsof neonatal HIE, major cellular and molecular mechanisms, potential therapies that are currently investigated either inpreclinical experimental animal models or in clinical trials in hypoxic ischemic brain injury in neonates