Neuroprotection of hypoxic/ischemic preconditioning in neonatal brain with hypoxic-ischemic injury

Abstract The neonatal brain is susceptible to hypoxic-ischemic injury due to its developmental characteristics. Hypoxia-ischemia means a decreased perfusion of oxygen and glucose, which can lead to severe encephalopathy. Although early initiation of therapeutic hypothermia was reported to provide neuroprotection for infants after HI, hypothermia administered alone after the acute insult cannot reverse the severe damage that already has occurred or improve the prognosis of severe hypoxic-ischemic encephalopathy. Therefore, exploring new protective mechanisms for treating hypoxic-ischemic brain damage are imperative. Until now, many studies reported the neuroprotective mechanisms of hypoxic/ischemic preconditioning in protecting the hypoxic-ischemic newborn brains. After hypoxia and ischemia, hypoxia-inducible factor signaling pathway is involved in the transcriptional regulation of many genes and is also play a number of different roles in protecting brains during hypoxic/ischemic preconditioning. Hypoxic/ischemic preconditioning could protect neonatal brain by several mechanisms, including vascular regulation, anti-apoptosis, anti-oxidation, suppression of excitotoxicity, immune regulation, hormone levels regulation, and promote cell proliferation. This review focused on the protective mechanisms underlying hypoxic/ischemic preconditioning for neonatal brain after hypoxia-ischemia and emphasized on the important roles of hypoxia inducible factor 1 signaling pathway.