Birth
asphyxia, which causes
hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world's 2.9 million
neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in
brain injury due to perinatal
asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies.
Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of
xenon and
melatonin have led to clinical phase I and II trials(1,2). The piglet HIE model is further used for neonatal
resuscitation- and hemodynamic studies as well as in investigations of
cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe
brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (< 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global
hypoxia-
ischemia is induced by lowering the inspiratory
oxygen fraction to achieve global
hypoxia,
ischemia through
hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of
cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure.
Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.