Differential effects of acute severe hypoxia and chronic sublethal hypoxia on the neonatal brainstem (pdf download available) anoxic brain injury causes

Perinatal asphyxia and neonatal chronic lung disease (CLD) are two major problems in newborn infants, often leading to neurodevelopmental deficits or disabilities later in life. Both problems are associated with hypoxia, but the nature of the hypoxia in the two problems is different. The hypoxia after perinatal asphyxia is often acute, severe or lethal, and associated with ischaemia of the brain. In contrast, the hypoxia in neonatal CLD is chronic or prolonged and sublethal. Such differences may exert differential effects on the functional integrity and development of the neonatal brain, leading to different neuropathological changes and neurodevelopmental outcomes.


In recent years, some investigators have studied the functional integrity of the neonatal auditory brainstem in infants after perinatal asphyxia and neonatal CLD and have found differences in the effects of acute severe hypoxia and chronic sublethal hypoxia on the neonatal brainstem.Anoxic brain injury causes in infants after perinatal asphyxia, neural conduction and synaptic function are impaired in both peripheral and central regions of the brainstem, although the impairment is slightly more severe in the more central than the more peripheral regions. In infants with neonatal CLD, however, neural conduction and synaptic function are impaired predominantly in the more central regions of the brainstem, whereas the more peripheral regions are relatively intact. These findings indicate that perinatal asphyxia affects both the central and peripheral regions of the brainstem, while neonatal CLD affects predominantly the central regions, without appreciable effect on the peripheral regions. This difference may be, at least partly, related to the different nature of hypoxia in the two clinical problems.Anoxic brain injury causes these findings shed light on the pathophysiology underlying neurological impairment and developmental deficits in neonatal CLD, related to chronic sublethal hypoxia, and after perinatal asphyxia, related to acute lethal hypoxia and the associated ischemia. The knowledge obtained from these studies also provides valuable information for studying and implementing neuroprotective interventions or therapies for the two neonatal problems. The interventions should target more central regions of the brain for infants with CLD, but target both peripheral and central regions of the brain for infants after perinatal asphyxia. Recent studies have also found that in infants with perinatal asphyxia, the electrophysiological activity in the neonatal brainstem is significantly depressed, suggesting major neuronal injury and/or neuronal death after severe hypoxia-ischemia.Anoxic brain injury causes for these infants there is a need to intervene with radical neuroprotective measures (e.G. Brain cooling) as early as possible to reduce further neuronal injury and death and rescue severely injured neurons. In infants with CLD, however, there was no noticeable depression of electrophysiological activity in the neonatal brainstem, suggesting no severe neuronal injury and/or neuronal death. It appears that for infants with CLD there is no need to implement radical treatments, and well regulated supplemental oxygen may remain the most valuable therapy, along with other therapeutic adjuncts.