Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review

Basilious, Alfred; Yager, Jerome Y.; Fehlings, Michael G.

doi:10.1111/dmcn.12599

Cited by 50 publications

(48 citation statements)

References 98 publications

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“…Although further studies and a systematic anthropometric analysis of individuals are needed to address this question, a recent systematic review of animal models that used uterine artery ligation to induce IUGR reached similar conclusions. Fetuses with growth restriction demonstrate a reduction in BW with relative sparing of brain mass and deficits in many neuroconductual tests (Basilious, Yager, & Fehlings, 2015). …”

Section: Discussionmentioning

confidence: 99%

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

et al. 2017

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IntroductionIntrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.MethodsUtero‐placental insufficiency was induced by meso‐ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry.ResultsPlacental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus.ConclusionsThe results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

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Section: Discussionmentioning

confidence: 99%

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

et al. 2017

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“…Several other models of IUGR are currently used, spanning many species, including chick embryos, rodents, and guinea pigs, as well as other methods in sheep. The advantages, disadvantages, and varying levels of severity of IUGR animal models have been well reviewed recently (8,56). The site of fetoplacental unit insult resulting in IUGR varies between models, as it does in human IUGR.…”

Section: Discussionmentioning

confidence: 99%

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Allison

Hooper

Coia

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Intrauterine growth restriction (IUGR) and preterm birth are frequent comorbidities and, combined, increase the risk of adverse respiratory outcomes compared with that in appropriately grown (AG) infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared with AG infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements, and/or increased ventilation-induced lung injury. IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury, and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. IUGR preterm lambs weighed 30% less than AG preterm lambs, with increased brain-to-body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared with AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth and had significant, but similar, increases in proinflammatory cytokine expression, lung injury markers, gene expression, and surfactant phosphatidylcholine species compared with unventilated controls. IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.

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“…Clinical studies suggest that placental transport capacity may be perturbed by maternal stress, owing to the utero-placental vascular dysfunction described in the previous section, which can impair bidirectional exchange of flow-limited substrates including oxygen and carbon dioxide (Myatt, 2006). The link between vascular function and nutrient delivery has been well established in uterine artery ligation models of placental insufficiency, where fetal hypoxia and oxidative stress are associated with reduced hippocampal size, abnormal neural migration, and hypomyelination in the offspring (Basilious et al, 2014;Lane et al, 2001;Reid et al, 2012). In addition, uterine artery ligation in rats disrupted striatal amino acid metabolism at term (Thordstein et al, 1992).…”

Section: Nutrient Exchange and Energy Homeostasismentioning

confidence: 99%

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

Bronson

Bale

2015

Neuropsychopharmacol

205

180

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Adversity experienced during gestation is a predictor of lifetime neuropsychiatric disease susceptibility. Specifically, maternal stress during pregnancy predisposes offspring to sex-biased neurodevelopmental disorders, including schizophrenia, attention deficit/hyperactivity disorder, and autism spectrum disorders. Animal models have demonstrated disease-relevant endophenotypes in prenatally stressed offspring and have provided unique insight into potential programmatic mechanisms. The placenta has a critical role in the deleterious and sex-specific effects of maternal stress and other fetal exposures on the developing brain. Stress-induced perturbations of the maternal milieu are conveyed to the embryo via the placenta, the maternal-fetal intermediary responsible for maintaining intrauterine homeostasis. Disruption of vital placental functions can have a significant impact on fetal development, including the brain, outcomes that are largely sex-specific. Here we review the novel involvement of the placenta in the transmission of the maternal adverse environment and effects on the developing brain.

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Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review

Cited by 50 publications

References 98 publications

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

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