Intrauterine growth restriction due to uteroplacental vascular insufficiency leads to increased hypoxia-induced cerebral apoptosis in newborn piglets

Burke, Christopher; Sinclair, Kate; Cowin, Gary; Rose, Stephen; Pat, Betty; Gobé, Glenda C.; Colditz, Paul B.

doi:10.1016/j.brainres.2006.04.129

Cited by 34 publications

(30 citation statements)

References 18 publications

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“…Hayashi et al (23) concluded that the MAPK7 pathway is critical for endothelial function and the maintenance of blood vessel integrity. In addition, a common cause of intrauterine growth restriction in humans is uteroplacental vascular insufficiency, which increases the incidence of perinatal asphyxia and neurodevelopmental disorders (24). A recent study showed that the cardiac dimensions are spared and may be used for gestational age estimation in growth-restricted fetuses resulting from uteroplacental insufficiency (25).…”

Section: Discussionmentioning

confidence: 99%

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

et al. 2015

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Abstract. Smith-Magenis syndrome (SMS) is a rare condition with multiple congenital malformations caused by the haploinsufficiency of RAI1 (deletion or mutation of RAI1). However, the correlation between genotype and phenotype is not well understood. The present study describes the prenatal diagnosis of monozygotic twins with a 17p11.2 deletion, which is indicative of SMS, who presented with discordant phenotypes and uteroplacental insufficiency. A high-resolution genome-wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in the 17p11.2 chromosome region. Accurate breakpoints of the deletion in these patients were used to identify correlations between SMS and the concomitant phenotypes, particularly uteroplacental insufficiency, which has rarely been investigated in SMS. In addition, no exonic mutations were identified in or affected known disease-associated loci that could explain the congenital anomalies, according to a model that accounts for the possibility of incomplete penetrance. Furthermore, a novel benign copy number variation (a duplication of 195 kb at 13q12.13) was identified but was unlikely to be clinically significant in the discordant phenotypes of the twins. The present study showed that multiple interacting genetic and environmental factors are involved in determining the variance of the SMS phenotype.

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Section: Discussionmentioning

confidence: 99%

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

et al. 2015

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“…To date, there are no reports of GABA A receptor protein expression in the piglet brain. In our laboratory, the piglet is an established animal model for studying the effect of hypoxia-ischemia, seizures and intra-uterine growth restriction in the perinatal brain [21,22,55]. The piglet is an appropriate model for perinatal research due to the many similarities in cardiovascular, metabolic and cerebral development to that of the human neonate [23].…”

Section: Introductionmentioning

confidence: 99%

Developmental Expression and Distribution of GABAA Receptor α1-, α3- and β2-Subunits in Pig Brain

Kalanjati

Miller²,

Ireland³

et al. 2011

Dev Neurosci

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The principal function of the γ-aminobutyric acid (GABA) system in the adult brain is inhibition; however, in the neonatal brain, GABA provides much of the excitatory drive. As the brain develops, transmembrane chloride gradients change and the inhibitory role of GABA is initiated and continues throughout juvenile and adult life. Previous studies have shown that GABA_A receptor subunit expression is developmentally regulated, and it is thought that the change in GABA function from excitation to inhibition corresponds to the changeover in expression of ‘immature’ to ‘mature’ subunit isoforms. We examined the protein expression pattern and distribution of GABA type A (GABA_A) receptor α₁-, α₃- and β₂-subunits in the parietal cortex and hippocampus of the developing piglet brain. Four perinatal ages were studied; 14 days preterm (P–14), 10 days preterm (P–10), day of birth (P0) and at postnatal day 7 (P7). Animals were obtained by either caesarean section or spontaneous birth. Protein expression levels and subunit localization were analysed by Western blotting and immunohistochemistry, respectively. In the cortex and hippocampus, GABA_A receptor α₁-subunit showed greatest expression at P7 when compared to all other age groups (p < 0.05). In contrast, α₃ expression in the cortex was elevated in preterm brain, peaking at P0, followed by a significant reduction by P7 (p < 0.05); a similar trend was observed in the hippocampus. GABA_A receptor β₂-subunit protein expression appeared relatively constant across all time points studied in both the cortex and hippocampus. Immunolabelling of the α₁-, α₃- and β₂-subunits was observed throughout all cortical layers at every age. GABA_A receptor α₃-subunit appeared to show specific localization to layers V and VI whilst labelling for the β₂-subunit was observed in layer IV. In the hippocampus of all animals, the α₁- and β₂-subunits were shown to immunolabel various cells and processes in the dentate gyrus (DG), CA1 and CA3; the α₃-subunit was barely observed except at the stratum moleculare of the DG. We report for the first time the ontogenesis of GABA_A receptor subunits α₁, α₃ and β₂ in the perinatal pig brain.

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“…Studies show that greater damage is seen in vulnerable brain areas, such as the hippocampus, brainstem and cortex, when asphyxia is encountered by the already IUGR fetus. Burke et al [2006] found that the dual insult of acute hypoxia in already IUGR fetuses resulted in a marked potentiation of expression of apoptotic marker in the brain of neonatal piglets. Similarly, IUGR human neonates that were exposed to a period of asphyxia due to placental infarction had increased brain injury [Burke and Gobe, 2005].…”

Section: Neuroactive Steroid Replacement Strategiesmentioning

confidence: 99%

Stress in Pregnancy: A Role for Neuroactive Steroids in Protecting the Fetal and Neonatal Brain

et al. 2009

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Stressors during pregnancy can lead to perinatal brain injury resulting in serious neurological impairment. Neuroactive steroid concentrations are elevated during pregnancy and are remarkably high in the fetal brain. In long-gestation species, including humans, these steroids enhance GABAergic inhibition and reduce the possibility of cerebral excitotoxicity during the last third of gestation. The fetal brain responds to acute hypoxia/ischemia by increasing steroid concentrations further as protection against excitotoxic cell death. The placenta has a key role in maintaining neuroactive steroid concentrations in the brain by acting as a source of precursors for neuroactive steroid synthesis. Gestational neuroactive steroid concentrations are needed for normal cell proliferation and cell death in the late gestation brain and a loss of these steroids at preterm birth may adversely affect development and vulnerability to injury.

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Intrauterine growth restriction due to uteroplacental vascular insufficiency leads to increased hypoxia-induced cerebral apoptosis in newborn piglets

Cited by 34 publications

References 18 publications

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

Developmental Expression and Distribution of GABA<sub>A</sub> Receptor α<sub>1</sub>-, α<sub>3</sub>- and β<sub>2</sub>-Subunits in Pig Brain

Stress in Pregnancy: A Role for Neuroactive Steroids in Protecting the Fetal and Neonatal Brain

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