Drugs for neuroprotection after birth asphyxia: Pharmacologic adjuncts to hypothermia

An adverse outcome is still encountered in 45% of full-term neonates with perinatal asphyxia who are treated with moderate hypothermia. At present pharmacologic therapies are developed to be added to hypothermia. In the present article, these potential neuroprotective interventions are described based on the molecular pathways set in motion during fetal hypoxia and following reoxygenation and reperfusion after birth. These pathways include excessive production of excitotoxins with subsequent over-stimulation of NMDA receptors and calcium influx in neuronal cells, excessive production of reactive oxygen and nitrogen species, activation of inflammation leading to inappropriate apoptosis, and loss of neurotrophic factors. Possibilities for pharmacologic combination therapy, where each drug will be administered based on the optimal point of time in the cascade of destructive molecular reactions, may further reduce brain damage due to perinatal asphyxia.