Developing a long-term surviving piglet model of neonatal hypoxic-ischemic encephalopathy

Abstract

Objective: This study was designed to develop a piglet model of neonatal hypoxic-ischemic encephalopathy, which would allow for serial assessments of long-term neurodevelopmental impairment.

Methods: In 12 newborn piglets, we produced hypoxia by 8% oxygen breathing for 5–91 minutes. We combined ischemia by reversible bilateral common carotid artery occlusion for varying times. Outcome measures were clinical neurological evaluation, magnetic resonance spectroscopy studies and brain histology.

Results: Those animals which received intravenous sedation and no mechanical ventilation showed poor tolerance to hypoxia-ischemia and died early in the course of the experiments. The use of inhalation anesthesia during surgical procedures and mechanical ventilation during hypoxia-ischemia was associated with long-term survival. Seven of eight animals that survived ≥ 48 hr showed clinical neurological abnormalities, that later resolved. Magnetic resonance spectroscopy measurements did not change significantly following hypoxia-ischemia. None of the animals had histopathological brain lesions.

Conclusion: When subjected to acute hypoxia-ischemia, piglets were likely to survive only if they were given such supportive measures as anesthesia and mechanical ventilation. Even with hypoxic-ischemic injury sufficient to produce acute signs of neurological dysfunctions, longterm, stable survival with no evident brain histopathological abnormalities was possible.

Keywords:

• PERINATAL ASPHYXIA
• BRAIN INJURY
• CEREBRAL PALSY