Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica

Abstract

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis.