Fetal asphyxia: short and long-term consequences and its role in preconditioning

Abstract

Asphyctic brain injury is a common and serious problem. It is a major cause of short and long-term neurological dysfunction in children and adults. Although the last few decades the knowledge in this scientific field has improved incredibly, there are still a lot of open issues that need to be resolved. The first part of this project investigated long-term changes in synaptic organization. Presynaptic bouton numbers and densities were analyzed, following 75 minutes of severe fetal asphyxia, induced by clamping the uterine and ovarian arteries. At the age of 19 months, fetal asphyctic animals showed a significant decrease in presynaptic bouton numbers and density in the striatum. In the fifth layer of the prefrontal cortex, on the contrary, a tendency towards an increase in presynaptic numbers was observed. Taken together, these results suggest that fetal asphyxia causes long-term, region-specific changes in presynaptic bouton numbers and density, probably by acceleration of the aging process. The second part of this project examined whether a mild fetal asphyctic insult can provide neuroprotection against a subsequent severe perinatal insult in rat pups. Mild fetal asphyxia was induced by clamping the uterine and ovarian arteries of the pregnant dam for 30 minutes. Rat pups with or without fetal asphyxia were then subjected to severe perinatal asphyxia was by immersing the uterine horns in a water bath for 18 minutes. Newborns, which underwent mild fetal asphyxia, had a tendency towards a lower mortality rate, a higher body weight and less TUNEL-positive cells in the striatum at postnatal day 8 compared to the newborns with severe perinatal asphyxia only. In conclusion, mild fetal asphyxia seemed to cause robust neuroprotection against severe perinatal asphyxia by lessening the number of delayed apoptotic cells. Therefore, down regulation of apoptotic cell death is probably one of the mechanisms involved in hypoxic-ischemic preconditioning.