The Fetal Response To Infection, With Particular Reference To Alterations Of Tryptophan Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$410,616.00
Summary
Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released f ....Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released from bacteria induce cells in the uterus and placenta to produce inflammatory chemicals that can damage the brain. In this project we propose the following model: 1), infection causes the release of substances from the uterus and placenta that disrupt the blood-brain barrier in the fetal brain; and, 2), infection alters the metabolism of the essential amino acid tryptophan in the fetus, causing greater production of metabolites that have toxic effects on the developing brain. We have preliminary evidence to support these two proposals. If the idea is proven correct, it should be possible to administer simple analogues of tryptophan to prevent the toxic metabolites of this amino acid from increasing in the fetus when either the mother or the uterus becomes infected. Because these substances can be given by mouth, this would allow a simple treatment to be developed for women at risk of infection, or who are already infected. This would be particularly useful wherever medical services and resources are limited, as for under-priviledged groups and in Third World countries.Read moreRead less
Mechanism Of Neurological Complications In Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$53,609.00
Summary
Malaria kills 1 million young children every year. About the same number are saved by treatment with anti-malarial drugs but have brain damage, leading to problems of understanding, learning or memory. The processes in the brain that lead to these changes are unknown. I will investigate a biochemical pathway that is activated during malaria infection, because I propose that this may cause the brain damage that leads to the long-term cognitive problems in survivors.