Table 1

Advantages and limitations of commonly used animal models

Animal	Advantages	Limitations	Examples of research findings
Rice–Vannucci rodent	Inexpensive and experiments can involve large numbers Extensive literature on baseline neurochemistry and behavioural assessment19 36 Suitable for short-term and long-term experimental outcomes At 10–14 days, CNS maturation considered to be comparable to a term human infant37	Small body size makes it difficult to accurately monitor multiple-organ function36 White matter maturation varies between species, most notably in the early postnatal days20 Postnatal CNS maturation is rapid36 and direct comparison of rat cerebral maturation on specific postnatal days to the gestational age of human infants can be challenging37	▸ Assessing neuroprotective impact of manipulating physiological parameters – Hypoglycaemia (deleterious) – Hypothermia (very protective) – Hypoxic preconditioning (protective) ▸ Evaluation of pathophysiological processes during hypoxia ischaemia (HI), eg, impact on the blood–brain barrier, cerebral blood flow and regional cerebral glucose utilisation38
Non-human primate	Closest phylogenic origin to human39 Body size sufficient to perform accurate physiological monitoring Model of HI can incorporate short-term physiological and biochemical outcomes as well as long-term behavioural outcomes	Very expensive model Unresolved ethical concerns in the use of higher-order animal species CNS of baboons and rhesus monkeys are more mature than a human newborn39	▸ Different patterns of injury are associated with the degree and duration of hypoxia/anoxia as well as the presence of acidosis5
Piglet	Well-established model with data on cerebral metabolic processes and histological analysis CNS maturation of piglet <48 h age is comparable to human neonate28 Body size sufficient to perform accurate physiological monitoring Relatively inexpensive	Animals mature rapidly, thus accuracy of postnatal age is important Severity of HI insult may be difficult to reproduce consistently36 Mostly suited to short-term analysis as long-term neurological outcome data are not well established	Cooling ameliorates secondary energy failure40 with a reduction in excitatory amino acid and nitric oxide release41 Cooling reduces degree of apoptosis rather than necrotic cell death42
Sheep/lamb	HI can be administered on catheterised lamb fetus in utero without prior anaesthesia24 36 Body size sufficient to perform accurate physiological monitoring Relatively inexpensive	Availability is restricted in some laboratories due to concerns regarding Q fever CNS of lambs is more mature than human newborns36, thus necessitating experiments to be performed in utero in order to model term human infants Mostly suited to short-term analysis as long-term neurological outcome data are not well established	▸ Secondary energy failure is accompanied by cytotoxic cellular oedema and excitotoxin release43 ▸ Selective head cooling for 72 h is safe and dramatically reduced cortical infarction and neuronal loss24

CNS, central nervous system; HI, hypoxia-ischaemia.