Neonatal hypoxic ischemic encephalopathy: An updated preclinical and clinical review

Abstract

Hypoxic-ischemic encephalopathy is a major cause of death and disability in the newborn period. Experimental models have demonstrated that brain injury in hypoxic-ischemic encephalopathy occurs in two phases: Primary energy failure and secondary energy failure. In primary energy failure, there is a cessation of oxidative metabolism and irreversible neuronal injury, followed by secondary energy failure due to glutamate release, elevation of intracellular calcium, reactive oxygen species formation, apoptotic cell death, and activation of the immune system. Secondary energy failure is the target of therapeutic intervention in neonatal hypoxic-ischemic encephalopathy. The sensitivities of cell types to hypoxic injury leads to the differences in injury pattern seen in term versus preterm infants. Current treatment recommendations include identification and treatment of seizures when present and prompt administration of therapeutic hypothermia if clinical parameters are met. This paper also discusses new treatment paradigms being developed, including erythropoietin, and the role of neuroimaging as a predictive tool for neurodevelopmental outcome.