title: Ibuprofen treatment for closure of patent ductus arteriosus is not associated with increased risk of neuropathology.
abstract: Ibuprofen is an effective pharmacological intervention for closure of a patent ductus arteriosus (PDA) in preterm infants and is an alternative to surgical ligation; however, it is not certain whether ibuprofen treatment is associated with adverse effects on the brain. Therefore, this study examined neuropathological outcomes of ibuprofen therapy for a PDA. Fetal baboons were delivered at 125 d of gestation (dg; term ∼185 dg) by caesarean section, given surfactant, and ventilated for 14 d with positive pressure ventilation (PPV). Baboons were randomly allocated to receive either ibuprofen (PPV+ ibuprofen, n = 8) or no therapy (PPV, n = 5). Animals were killed on day 14 and brains assessed for cerebral growth, development, and neuropathology. Body and brain weights, the total volume of the brain, and the surface folding index (measure of brain growth) were not different (p > 0.05) between PPV+ ibuprofen-treated and PPV animals. There was no difference (p > 0.05) in the number of myelin basic protein-immunoreactive (IR) oligodendrocytes, glial fibrillary acid protein-IR astrocytes, or Iba1-IR macrophages/microglia in the forebrain. No overt cerebellar alterations were observed in either group. Ibuprofen treatment for PDA closure in the preterm baboon neonate is not associated with any increased risk of neuropathology or alterations to brain growth and development.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia. m.loeliger@unimelb.edu.au
authors.forename: Michelle
authors.initials: M
authors.lastname: Loeliger
authors.forename: Amy
authors.initials: A
authors.lastname: Shields
authors.forename: Donald
authors.initials: D
authors.lastname: McCurnin
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
authors.forename: Bradley
authors.initials: B
authors.lastname: Yoder
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Inder
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Rees
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007052:Ibuprofen / Q000009:adverse effects / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010215:Papio; D011175:Positive-Pressure Respiration; D047928:Premature Birth; D011663:Pulmonary Surfactants / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D005904:Glial Fibrillary Acidic Protein; D011663:Pulmonary Surfactants; D007052:Ibuprofen