Pathophysiology of hypoxic–ischemic encephalopathy: a review of the past and a view on the future

Hypoxic–ischemic encephalopathy, also referred as HIE, is a type of brain injury or damage that is caused by a lack of oxygen to the brain during neonatal period. The incidence is approximately 1.5 cases per 1000 live births in developed countries. In low and middle-income countries, the incidence is much higher (10‒20 per 1000 live births). The treatment for neonatal HIE is hypothermia that is only partially effective (not more than 50% of the neonates treated achieve an improved outcome). HIE pathophysiology involves oxidative stress, mitochondrial energy production failure, glutaminergic excitotoxicity, and apoptosis. So, in the last years, many studies have focused on peptides that act somewhere in the pathway activated by severe anoxic injury leading to HIE. This review describes the pathophysiology of perinatal HIE and the mechanisms that could be the target of innovative HIE treatments.