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Using animal models to improve care of neonatal encephalopathy
  1. Ingran Lingam,
  2. Adnan Avdic-Belltheus,
  3. Nicola J Robertson
  1. Institute for Women's Health, University College London, London, UK
  1. Correspondence to Professor Nicola J Robertson, Professor of Perinatal Neuroscience and Honorary Consultant Neonatologist, Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, UK; n.robertson{at}ucl.ac.uk

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Introduction

Neonatal encephalopathy (NE) is responsible for a significant burden of disability and death worldwide.1 The use of animal models in the study of perinatal hypoxia-ischaemia (HI) has a history of over 200 years; studies initially showed that the premature animal is more tolerant of asphyxia than a term animal, which is in turn more resistant to asphyxia than an adult.2 ,3 In the 1950s to the 1970s, studies in the primate model showed that the pattern of brain injury was clearly influenced by the severity and type of HI; these studies led to a description of two patterns of injury, namely acute total asphyxia4 and chronic partial asphyxia.5 In the last 30 years, progress was made by using animal models of NE to understand the timing and evolution of brain injury after HI. Triggered by the observation in human babies that brain energy metabolism on phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) transiently recovered after birth and declined in the subsequent hours and days after birth despite intensive care support,7 studies in the newborn piglet8 and rat9 allowed pathophysiology and timing of events after HI to be studied more precisely than in the human fetus and neonate. Establishing the timing of this ‘secondary’ energy failure led to the concept that a window of opportunity existed whereby an intervention started after the primary insult could alter the trajectory of brain damage. The translation of the ideas and questions from bedside to bench moved therapeutic hypothermia from a research hypothesis to standard clinical care6 (figure 1). Optimising neonatal neuroprotection beyond therapeutic hypothermia requires further preclinical research with careful thought in using appropriate animal models to ensure efficacy, safety and translatability of the findings.

Figure 1

Key milestones. MRS, magnetic resonance spectroscopy.

Factors to consider for translation of animal studies to humans

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