ABSTRACT
OBJECTIVE: Pentoxifylline (PTX) has immunomodulatory properties and is known to reduce sepsis-associated infant mortality. We aimed to evaluate maternal oral and intra-amniotic administration of PTX for the prevention of fetal inflammation and injury in a caprine model. MATERIALS AND METHODS: Inflammation-mediated fetal injury was induced with maternal granulocyte-colony stimulating factor and intra-amniotic endotoxin at 0.76 of gestation in date-mated pregnant goats. Eight groups were formed (n=4 each): Control, fetal injury, oral 30 mg/kg/day and 60 mg/kg/day PTX for 15 days + fetal injury, intra-amniotic 400 mg/kg and 800 mg/kg estimated fetal weight single-dose PTX with and without fetal injury. Preterm delivery by hysterotomy was performed at 0.80 of gestation to evaluate the fetal and placental effects. Immunochemistry for various markers including interleukins, caspases, cyclooxygenases, vimentin, myelin basic protein, and surfactant proteins were carried out in the fetal lungs, fetal brain, and placenta. Fetal plasma and amniotic fluid interleukins were also evaluated. Kruskal-Wallis H test and Mann-Whitney U test were used for comparisons. RESULTS: High-dose (60 mg/kg/day) maternal prophylactic oral treatment attenuated endotoxin-related histological injury and was related to low inflammatory marker expressions comparable to the controls (p>0.05 except cyclooxygenase 2). Following maternal oral administration, fetal plasma and amniotic fluid levels of the studied interleukins were also lower than the untreated endotoxin-exposed animals (p<0.05 for all comparisons). Intra-amniotic PTX was associated with inconsistent results and increased inflammatory markers in some fetuses. CONCLUSION: Oral PTX before preterm birth mitigates intrauterine inflammation with neuroprotective effects in the fetus. PTX can be considered as a candidate drug for fetal brain injury prevention in the preterm period.
ABSTRACT
OBJECTIVE: To define a novel experimental model with maternal intravenous (i.v.) granulocyte-colony stimulating factor (G-CSF) followed by a single- and high-dose of 20 mg intra-amniotic (IA) endotoxin to induce fetal brain injury in the preterm fetal goat. MATERIALS AND METHODS: Pregnant goats (n=4) were given 50 microg/day G-CSF into the maternal jugular vein through gestational days 110-115 (term, 150 days). At gestational day 115, 20 mg of IA endotoxin was administered. Following preterm delivery at day 120 by cesarean section umbilical cord, fetal lung and brain tissues were harvested for histopathology, immunohistochemistry, and electron microscopy. Inflammatory markers were evaluated in the amniotic fluid and fetal plasma. RESULTS: Necrotizing funisitis with abundant leukocyte infiltration and fetal brain injury was induced in all the fetuses in the experimental group. CONCLUSION: Maternal i.v. G-CSF for 5 days followed by 20 mg of IA endotoxin is a feasible caprine model to exacerbate intrauterine inflammation.
