Researchers from University College London, Hopital Robert Debre, and Universite Paris Diderot, Paris assessed the neuroprotective effects of melatonin combined with therapeutic hypothermia after transient hypoxia-ischemia in a piglet model of perinatal asphyxia. Melatonin administered intravenously 10 min after transient hypoxia-ischemia and repeated at 24 hr augments hypothermic neuroprotection based on improved cerebral energy metabolism, using magnetic resonance spectroscopy biomarkers and continuous EEG monitoring. The piglet model of H-I resembles the clinical setting in a neonatal intensive care unit. The observed benefits and safety profile of melatonin support consideration of phase I and II clinical studies of melatonin-augmented therapeutic hypothermia for neonatal encephalopathy. 
COMMENT. Melatonin (N-acetyl-5-methoxytryptamine), a naturally occurring hormone secreted by the pineal gland, when administered alone has neuroprotective actions against H-I brain injury in animal models. The present study demonstrates that melatonin augments the neuroprotective effect of hypothermia.