The Newborn Pig Global Hypoxic-Ischemic Model of Perinatal Brain and Organ Injury

Abstract

Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and is a major contributor of disability. Animal models have contributed greatly to the understanding of the pathophysiology of HIE such as the mode of cell death, secondary energy failure, and the development of therapeutic interventions such as therapeutic hypothermia. Further research into the understanding of pathophysiology of HIE and neuroprotective interventions is required. The newborn pig global hypoxic-ischemic model of perinatal brain and organ injury is a valuable model simulating neonatal encephalopathy secondary to perinatal asphyxia in newborn term babies. This model involves induction of global hypoxia-ischemia to the whole body for 45 min while monitoring brain activity. In this model, reduction of inhaled oxygen to 6–7 % induces hypoxia and significant hypotension is induced by halothane anesthesia leading to ischemia. The pigs manifest clinical signs of encephalopathy including seizures and multiorgan dysfunction including hypotension and histopathological injury in the lungs, heart, kidneys, and the liver. This is a survival model; the pigs survive after receiving full intensive care in the acute period at the same level as that of asphyxiated newborns. The model is suitable to assess the effect of neuroprotective interventions on neurological recovery and on all organs in particular the brain.