3 Queensland Brain Institute
Background: The preterm infant has an underdeveloped antioxidant system and impaired energy production, which is further compromised in the presence of inflammation. Increased tissue creatine levels may protect the preterm fetus exposed to chorioamnionitis as creatine plays an essential role in energy production through the shuffling of phosphate groups to form ATP and has antioxidant and anti-inflammatory properties. The preterm fetus is likely deficient in creatine: creatine supplementation during this vulnerable developmental period could prevent energy deficits, subsequent inflammatory cascade and resultant tissue damage. We will test the neuroprotective effects of antenatal creatine loading of the fetus in a preterm lamb model of chorioamnionitis.
Hypothesis: We hypothesise that creatine loading of the fetus will protect against damage caused by a pro-inflammatory stimulus (intra-amniotic lipopolysaccharide), such as reduced brain volumes, increased markers of oxidative stress, inflammation and injury in the developing brain.
Methods: Ewes underwent hysterotomy at 90 days gestation to implant fetal loggers, intravenous catheters and an amniotic catheter. Creatine (6 mg/kg/h) or saline was infused (IV) from gestational age (GA) 94 to 111 days. A pro-inflammatory stimulus (LPS 1 mg) or saline was delivered into the amniotic fluid at 104 d GA. The left hemisphere was fixed in 4 % paraformaldehyde and will be scanned using MRI to be analysed for volume differences and neuropathology scoring, as well as for markers of injury and inflammation using immunohistochemistry. The right hemisphere was snap frozen to be used in assays assessing oxidative stress, inflammatory markers and mitochondrial function.
Results and Significance:
This study will provide vital data to support clinical trials to improve neurological outcomes in preterm infants exposed to proinflammatory stimuli such as chorioamnionitis.