ABSTRACT
Premature infants now have an improved chance of survival, but the impact of respiratory therapies on the brain, particularly the cerebellum, remains unclear. We examined the effects of early nasal continuous positive airway pressure (EnCPAP) ventilation and delayed (Dn) CPAP on the development of the cerebellum in prematurely delivered baboons. The baboons were delivered at 125 +/- 2days of gestation and ventilated for 28 days with either EnCPAP commencing at 24 hours (n = 5) or DnCPAP commencing at 5 days (n = 5). Gestational controls (n = 4) were delivered at 153 days. Cerebella were assessed histologically, and an ontogeny study (90 days to term) was performed to establish values for key cerebellar developmental indicators. Cerebellar weight was reduced in DnCPAP but not EnCPAP animals versus controls; cerebellar/total brain weight ratio was increased in EnCPAP (p < 0.05) versus control and DnCPAP animals. There was no overt damage in the cerebella of any animals, but a microstructural alteration index based on morphological developmental parameters and microglial immunoreactivity was increased in both prematurely delivered cohorts versus controls (p < 0.001) and was higher in DnCPAP than EnCPAP animals (p < 0.05). These results indicate that respiratory regimens can influence cerebellar development and that early compared with delayed extubation to nCPAP seems to be beneficial.
Subject(s)
Cerebellum/abnormalities , Cerebellum/physiopathology , Premature Birth/pathology , Premature Birth/therapy , Respiration, Artificial/methods , Animals , Blood Pressure/physiology , Body Weight , Calcium-Binding Proteins/metabolism , Cell Proliferation , Cerebellum/pathology , Disease Models, Animal , Female , In Situ Nick-End Labeling/methods , Ki-67 Antigen/metabolism , Nerve Tissue Proteins/metabolism , Oligodendroglia/metabolism , Oligodendroglia/pathology , Organ Size , Papio , Pregnancy , Premature Birth/physiopathology , Purkinje Cells/metabolism , Purkinje Cells/pathology , Respiration , Time FactorsABSTRACT
A patent ductus arteriosus (PDA) alters pulmonary mechanics and regional blood flow in the preterm infant. Its significance with respect to brain injury and brain development are unclear. We evaluated the effects of surgical ductal ligation on the preterm baboon brain. Baboons were delivered at 125 d of gestation (dg, term approximately 185 dg) and ventilated for 14 d (n = 12). The PDA was ligated 6 d after delivery (n = 7) or left untreated (n = 5). Animals were euthanized at 139 dg and brains compared histologically with gestational control fetuses (n = 7) at 140 dg. Brain and body weights were reduced (p < 0.05) in both groups of ventilated preterm animals; however, the brain to body weight ratio was increased (p < 0.01) in ligated, but not unligated newborns compared with gestational controls. No overt lesions were observed in either premature newborn group. Astrocyte density in the neocortex and hippocampus were greatest in the unligated newborns (p < 0.01). Myelination and oligodendrocytes were reduced (p < 0.05) in both premature newborn groups. The brain growth and development index was reduced, and the damage index was increased in prematurely delivered baboons. Surgical ligation of the PDA does not increase the incidence of brain injury and may be beneficial if the PDA is contributing to persistent pulmonary and hemodynamic instability.
Subject(s)
Brain/pathology , Cardiac Surgical Procedures , Ductus Arteriosus, Patent/surgery , Premature Birth , Animals , Animals, Newborn , Apoptosis , Astrocytes/pathology , Body Weight , Brain/blood supply , Brain/growth & development , Cell Proliferation , Ductus Arteriosus, Patent/pathology , Ductus Arteriosus, Patent/physiopathology , Female , Gestational Age , Hemodynamics , Hippocampus/pathology , Ligation , Neocortex/pathology , Oligodendroglia/pathology , Organ Size , Papio papio , Pregnancy , Respiration , Respiration, Artificial , Time FactorsABSTRACT
Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes. Pregnant sheep were infused intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116, 117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days). Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were measured before and after each infusion. Compared with controls, ethanol exposure reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I (-35%) at 30 h, and decreased fetal plasma IGF-II (-28%) from 24 to 54 h after the first infusion. Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We conclude that suppression of maternal and fetal IGF abundance may contribute to fetal growth restriction induced by acute or binge ethanol exposure.
