Erythropoietin as a Neuroprotectant for Neonatal Brain Injury: Animal Models

Prematurity and perinatal hypoxia-ischemia are common problems that result in significant neurodevelopmental morbidity andhigh mortality worldwide. The Vannucci model of unilateral brain injury was developed to model perinatal brain injury dueto hypoxia-ischemia. Because the rodent brain is altricial, i.e., it develops postnatally, investigators can model eitherpreterm or term brain injury by varying the age at which injury is induced. This model has allowed investigators to betterunderstand developmental changes that occur in susceptibility of the brain to injury, evolution of brain injury over time,and response to potential neuroprotective treatments. The Vannucci model combines unilateral common carotid artery ligationwith a hypoxic insult. This produces injury of the cerebral cortex, basal ganglia, hippocampus, and periventricular whitematter ipsilateral to the ligated artery. Varying degrees of injury can be obtained by varying the depth and duration of thehypoxic insult. This chapter details one approach to the Vannucci model and also reviews the neuroprotective effects of erythropoietin(Epo), a neuroprotective treatment that has been extensively investigated using this model and others.