New Pharmacological Approaches in Infants with Hypoxic-Ischemic Encephalopathy

Giuseppe      Buonocore; Serafina      Perrone; Giovanni      Turrisi; Boris      W. Kramer; Walter      Balduini

doi:10.2174/1381612811209023086

Abstract

New knowledge of the pathophysiology and evolution of hypoxic-ischemic brain injuries has made feasible interventions to improve clinical outcomes for newborns surviving birth asphyxia. Brain injury following hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. The specific pathologic processes preceding the onset of irreversible cerebral injury appear to be a combination of several mechanisms that are variable according to the severity and duration of the insult and to biochemical modifications in the brain. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy, as well as to predict their outcome. The role of oxidative stress in newborn morbidity with respect to the higher risk of free radical damage in these babies is growing. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Potential neuroprotective strategies targeting different pathways leading to neuronal cell death in response to hypoxic-ischemic insult have been investigated: hypothermia, erythropoietin, iminobiotin, deferioxamine, magnesium, allopurinol, xenon, melatonin and statins. Hypothermia is currently the only recognized beneficial therapy. However, many infants still develop significant adverse outcomes. It is becoming evident that the association of moderate hypothermia with neuroprotective drugs may enhance the outcome. By virtue of their pleiotropic effects without toxic effects, melatonin and statins may act at different levels of the multiple mechanisms responsible for the progression of the neurodegenerative process and represent promising neuroprotectants, alone or as additional adjunctive therapy, for reducing brain injury and its long-term sequelae in infants. More clinical studies are needed to clarify the role of these potential neuroprotective drugs.

Keywords: Newborn infant, hypoxic-ischemic encephalopathy, birth asphyxia, brain injury, oxidative stress, neuroprotection, biochemical modifications, melatonin, statins, adjunctive therapy