Role Of Kynurenine Metabolites In Causing And Preventing Excitotoxic Brain Damage In The Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$92,815.00
Summary
Brain damage is present in some babies at birth, and recent epidemiological and clinical studies strongly suggest that this either occurs some time during the pregnancy, or the conditions are such that the fetal brain is particularly vulnerable to the stresses that are present during labor and birth. In this project we propose that hypoxic (low oxygen) conditions in the womb, either alone or in combination with substances released because of maternal infection, cause accumulation of a neurotoxic ....Brain damage is present in some babies at birth, and recent epidemiological and clinical studies strongly suggest that this either occurs some time during the pregnancy, or the conditions are such that the fetal brain is particularly vulnerable to the stresses that are present during labor and birth. In this project we propose that hypoxic (low oxygen) conditions in the womb, either alone or in combination with substances released because of maternal infection, cause accumulation of a neurotoxic substance - QUINOLINIC ACID - in the fetal brain and circulation. The increased production of QUINOLINIC ACID occurs because certain cells react to the low oxygen and infectious conditions - these cells include MICROGLIA, a cell type in the brain. Little is currently known about MICROGLIA in the developing brain. We will therefore study the effects of hypoxia and infection in fetal sheep, and we will determine how these conditions affect MICROGLIA and the synthesis of QUINOLINIC ACID in the fetal brain. The capacity of the brain to produce QUINOLINIC ACID is closely related to the dietary intake of the essential amino acid TRYPTOPHAN, and it is decreased when synthetic analogues of tryptophan are infused. Therefore, we have devised a treatment regime using these tryptophan analogues to prevent increases of QUINOLINIC ACID concnetrations in the fetal brain, and we propose that a simple treament is at hand to reduce the incidence of perinatal brain damage in human pregnancies.Read moreRead less
Preterm birth, a birth before the 37th week of pregnancy occurs for fewer than 8% of mothers but is associated with two-thirds of all fetal deaths and deaths of liveborn infants in the first month after birth. In the late 1990s those deaths are concentrated among very preterm births i.e. births before the 32nd week of pregnancy. Infants born very preterm are very likely to need neonatal intensive care, quite likely to have had major respiratory, infectious or other problems after birth, and to n ....Preterm birth, a birth before the 37th week of pregnancy occurs for fewer than 8% of mothers but is associated with two-thirds of all fetal deaths and deaths of liveborn infants in the first month after birth. In the late 1990s those deaths are concentrated among very preterm births i.e. births before the 32nd week of pregnancy. Infants born very preterm are very likely to need neonatal intensive care, quite likely to have had major respiratory, infectious or other problems after birth, and to need readmission to hospital in the first year after birth. Surviving infants are more likely to have major impairments, minor impairments, and school difficulties than infants born at term. There is a substantial impact on families, health services and society of very preterm birth.There has been no reduction in the proportion of births which are preterm, or very preterm in the last 20 years, though advances in treatment and care have markedly improved the survival of preterm and very preterm infants. This study will investigate the role of previous pregnancies which did not result in births (miscarriages and terminations), together with other procedures such as D and C (dilatation and curettage), in subsequent preterm birth. As these previous pregnancy losses are all fairly common experiences any associated risk is important and this particular factor has not been studied in this way before. There is preliminary evidence that they may be associated with preterm birth and the study will be able to measure the associations while taking into account all the other known risk factors. Other possible risk factors such as experiencing violence in pregnancy or social factors acting at a neighbourhood level will also be included. If it is found that previous pregnancy losses are independently associated with preterm birth it will be possible to develop and test preventive strategies.Read moreRead less
This research investigates the factors regulating the transition of the lung from the fluid filled organ in fetal life to the air filled organ required at birth. Many preterm babies fail this transition and in order to survive, their lungs often require mechanical ventilation, which has been suggested to cause lung injury. Using synchrotron generated X-rays, we can determine how particular resuscitation techniques are able to reduce this injury and promote aeration at birth.