ASPHYXIAL BRAIN-DAMAGE IN THE NEWBORN - NEW INSIGHTS INTO PATHOPHYSIOLOGY AND POSSIBLE PHARMACOLOGICAL INTERVENTIONS

New insights into the pathophysiology of the hypoxic-ischemic insult have opened the possibility of pharmacologic intervention in neonatal hypoxic-ischemic encephalopathy. It is now known that many neurons survive a hypoxic-ischemic insult but remain dysfunctional for hours, with profound alterations in cell function. A cascade of biochemical alterations occurs as a consequence of cellular ionic shifts, energy depletion, degradation of cell membrane phospholipids, and increased release of neurotransmitters. In addition, there are alterations in the metabolism of arachidonic acid and prostanoids and an excessive production of oxygen free radicals. The new therapeutic modalities are aimed at preventing or arresting the biochemical changes that occur in the period after hypoxia-ischemia. This review details the biochemical alterations associated with neonatal hypoxic-ischemic encephalopathy and discusses the possible use in newborns of pharmacologic agents currently undergoing extensive investigations in experimental animals and adult humans.