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.