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Biomedical subjects

Megan Cock

Publications and source records attributed to Megan Cock.

6 recordsLinked to original sources
PubMed2007

Vulnerability of dopaminergic amacrine cells and optic nerve myelination to prenatal endotoxin exposure.

PURPOSE: Intrauterine infection has been linked to preterm delivery and neurologic injury. The purpose of this study was to investigate the effects of fetal inflammation induced by exposure to endotoxin on the structure and neurochemistry of the retina and optic nerve. METHODS: The bacterial endotoxin, lipopolysaccharide (LPS), was administered to fetal sheep at approximately 0.65 of the approximately 147-day gestation period via repeated bolus doses (1 microg/kg per day) over 5 days, with fetal retinas and optic nerves assessed 10 days after the first LPS exposure. RESULTS: In the retina, the total number of tyrosine hydroxylase immunoreactive (TH-IR), dopaminergic amacrine cells was reduced (P < 0.05) in LPS-exposed compared with control fetuses. There was no difference in the number of ChAT-, substance P-, or NADPH-d-positive amacrine cells. The total number of myelinated axons in the optic nerve was not different (P > 0.05) between groups; however, the myelin sheath was thinner (P < 0.05) in LPS-exposed fetuses. CONCLUSIONS: Prenatal exposure to repeated doses of endotoxin results in alterations to the retina and optic nerve with specific effects on dopaminergic neurons and myelination, respectively. These findings could have implications for visual function.

Amacrine Cells↗
PubMed2005

Pulmonary function and structure following mild preterm birth in lambs.

Our objective was to determine whether postnatal respiratory function, lung growth, and lung structure are affected by preterm birth which did not require neonatal respiratory support. Two groups of preterm (P) lambs were delivered 2 weeks before term, at 133 days of gestational age (GA). Tissue was collected at term equivalent age (TEA, 147 days GA) in one P group and at 6 weeks post-TEA in the other. Tissue was also collected from control (C) lambs soon after term birth (TEA) and at 6 weeks post-TEA. Lung function was assessed at TEA and 6 weeks post-TEA. Respiratory system compliance (Crs/kg BWT) was not different between P and C groups at TEA, but was higher (P = 0.02) in P lambs at 6 weeks post-TEA. Pulmonary resistance was 62% higher in P lambs than controls (P = 0.07) at TEA, and remained higher at 6 weeks post-TEA. Lung weights (wet and dry) were greater (P < 0.05) in preterm animals at both ages; when adjusted for body weight, only dry lung weight remained higher at 6 weeks post-TEA. Alveoli were more numerous (P = 0.05) and smaller (P = 0.05) in preterm lambs compared to controls at both ages. Alveolar septa were 33% thicker and the blood-air barrier was 26% thicker in P lambs than in controls at TEA, and remained thicker at 6 weeks post-TEA. In P lambs, the airway epithelium was thicker at TEA and 6 weeks post-TEA. At TEA, pulmonary tropoelastin expression was 27% lower in P lambs. At 6 weeks post-TEA, dry lung weight and lung protein content were approximately 50% greater in preterm lambs than in controls (P < 0.05), whereas lung DNA, elastin, and collagen contents were similar in the two groups. We conclude that mild preterm birth per se leads to both transient and persistent changes in lung development. Persistent increases in lung protein content and in the thickness of the airway epithelium, and a greater number of smaller alveolar, may alter later lung function.

Animals↗
PubMed2005

Fetal growth restriction induced by chronic placental insufficiency has long-term effects on the retina but not the optic nerve.

PURPOSE: Reduced birth weight is associated with an increased risk of visual impairments. This study was undertaken to determine whether prenatal exposure to a chronic compromise sufficient to cause fetal growth restriction (FGR) results in long-term alterations to the retina and optic nerve. METHODS: FGR was induced by umbilicoplacental embolization (UPE) in two cohorts of pregnant ewes from (1) 120 days of gestation (dg) until 140 dg and (2) 120 dg until term ( approximately 147 dg). Control fetuses were not subjected to UPE. The structure and neurochemistry of the retina and number and structure of ganglion cell axons were assessed in near-term (140 dg) and adult animals (2.3 years). RESULTS: In near-term FGR fetuses compared with control fetuses there were significant reductions (P < 0.05) in the outer plexiform layer (OPL), the photoreceptor inner and outer segment layers, the inner nuclear layer (INL) in the central retina and the outer nuclear layer (ONL) in the peripheral retina, and the diameter of ganglion cell axons in the optic nerve, with a proportional reduction in the thickness of myelin sheaths. In FGR animals compared with the control at 2.3 years, there were significant reductions (P < 0.05) in the total thickness of the retina, the thickness of the photoreceptor outer segment layer and the INL and the number of tyrosine hydroxylase-immunoreactive (TH-IR) dopaminergic amacrine cells. Axonal diameter and myelin sheath thickness in the optic nerve were not different (P > 0.05) between groups. CONCLUSIONS: Chronic placental insufficiency in late gestation results in long-lasting effects on specific retinal components, including photoreceptor outer segments and TH-IR amacrine cells. Other alterations observed at term, including reductions in growth and myelination of optic nerve axons, do not persist, suggesting delayed rather than permanently compromised development. Alterations persisting into adulthood could affect visual function.

Amacrine Cells↗
PubMed2003

The fetal brainstem is relatively spared from injury following intrauterine hypoxemia.

Our aim was to test the hypothesis that the fetal brainstem is relatively spared, compared to other brain regions, from hypoxia-induced damage. We have used established experimental models of acute and chronic intrauterine compromise in sheep to mimic conditions that can arise in human pregnancy. The acute insult was 12 h of placental insufficiency induced by restricted utero-placental blood flow at 90 days of gestation (term approximately 147 days). Five weeks after this insult (n=7 fetuses) there was no overt damage to the brainstem nor were there alterations to the blood vessel morphology, volume of the medulla or of medullary nuclei compared to controls (n=8). This regimen is known to have significant effects on the forebrain and cerebellum. The chronic insult was induced in five fetuses via embolisation of the umbilico-placental circulation from 120 to 140 days of gestation. An additional three fetuses were found to be spontaneously hypoxemic (SH) immediately after surgery. At 140 days, in brainstems of all chronically hypoxemic fetuses compared to controls (n=8), there was an increase (P<0.05) in the percentage of neuropil occupied by blood vessels and abnormal myelin in the most severely SH fetus but no other morphological or neurochemical alterations. This regimen is known to cause marked damage to the cerebral hemispheres and to a lesser extent to the cerebellum. We suggest that the absence of marked structural or neurochemical alterations in the brainstem is most likely due to the maintenance of oxygen delivery to the brainstem during fetal hypoxemia.

Animals↗
PubMedDate not supplied

Altered airway responsiveness in adult sheep born prematurely: effects of allergen exposure.

The aim of this study was to determine the effects of preterm birth per se on airway function in adult sheep. Preterm birth was induced at approximately 0.89 of term. At approximately 1 year of age the authors measured pulmonary resistance (RL) and airway responsiveness before and after house dust mite (HDM) challenge. Mature preterm sheep tended to have greater baseline RL than controls (P = .12): the smaller preterm sheep showed significantly greater RL than controls following bronchoconstrictor challenge. Preterm animals tended to have greater baseline total blood leukocyte count (P = .06). It was concluded that preterm sheep, especially with low postnatal growth, have greater airway responsiveness to bronchoconstrictor and higher baseline RL.

Airway Resistance↗