Lay summary
Low oxygen and impaired blood supply to the brain (hypoxia-ischaemia, (HI)) around birth is associated with death, brain damage and disability in about 2/1000 live term births in New Zealand. Brain cooling (therapeutic hypothermia (TH)) is now well established to improve survival without disability but is only partially effective and must be started within 6 hours of birth. Thus, the challenge is to find treatments to augment hypothermic neuroprotection as well as neuroprotective treatments that have a longer window of opportunity for effective intervention. Recent evidence suggests that the type 2 diabetes mellitus drug, exendin-4, has neuroprotective properties but this has not been demonstrated in large animal translational models. Excitingly, our preliminary data in fetal sheep, suggest that exendin-4 significantly improves the recovery of brain activity after hypoxia ischaemia and critically, augments neuroprotection with therapeutic hypothermia.