Neurodevelopmental Effects of Undernutrition and Placental Underperfusion in Fetal Growth Restriction Rabbit Models

Illa, M.; Eixarch, Elisenda; Muñoz‐Moreno, Emma; Batalle, Dafnis; Leal‐Campanario, Rocío; Gruart, Agnès; Delgado‐García, José M.; Figueras, F.; Gratacós, E.

doi:10.1159/000454859

Cited by 18 publications

(28 citation statements)

References 39 publications

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“…MRI results support previous findings in the rabbit model showing impaired global network infrastructure, integration, and segregation evidenced by a reduction in FA-weighted strength as well as global and local efficiencies [13,28]. Likewise, alterations in brain networks have been previously described in humans to persist in childhood and early adolescence [11,12,14,36].…”

Section: Discussionsupporting

confidence: 90%

“…On the one hand, the rabbit brain shows a timing of perinatal brain white matter maturation closer to that of humans compared to other species [26]. Regarding the IUGR model, the perinatal results as well as the reported neonatal and long-term neurodevelopmental impairments are in good agreement with the literature for this model [13,24,28,29] and also with clinical observations [2][3][4][5][6]8]. Regarding histological assessment, DSs are plastic structures and are constantly subjected to external inputs [57].…”

Section: Discussionsupporting

confidence: 79%

“…In the control group, due to the high number of animals eligible to be evaluated (n = 24), only a subsample was included in this analysis (n = 13). In order to assess learning skills, the Skinner test was applied as previously described [28]. Learning was considered when the animal pressed the lever and went directly towards the food dispenser at least three different times in the same session.…”

Section: Functional Testing Protocol and Sample Collectionmentioning

confidence: 99%

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Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

Illa¹,

Brito²,

Pla³

et al. 2017

Fetal Diagn Ther

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Introduction: The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. Materials and Methods: IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. Results: IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. Conclusions: IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 79%

Section: Functional Testing Protocol and Sample Collectionmentioning

confidence: 99%

See 1 more Smart Citation

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

Illa¹,

Brito²,

Pla³

et al. 2017

Fetal Diagn Ther

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“…Among the various particle types, we found airborne copper to be associated with tissue modifications and functional connectivity in the caudate nucleus in children . Other metals, such as iron, have been linked to structural changes in mice brain, and environmental Fe nanoparticles were found in brain tissue . Furthermore, two recent studies in rats exposed to NO 2 (an urban gas) reported clear evidence of brain damage, suggesting a specific neurotoxicity of NO 2 .…”

Section: Why To Investigate Air Pollution?mentioning

confidence: 71%

Pre‐natal brain development as a target for urban air pollution

Sunyer

Dadvand

2019

Basic Clin Pharma Tox

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Air pollution is the main urban‐related environmental hazard and one of the major contributors to the global burden of disease based on its cardiovascular‐respiratory impacts. In children, exposure to urban air pollution is associated, among others, with decelerated neurodevelopment early in life and increased risk of neurodevelopmental problems such as attention‐deficit hyperactivity disorder, autism spectrum disorders, academic failure and the start of Alzheimer's pathogenesis. However, the evidence of the effects of air pollution on brain development is still inadequate, mainly due to the limitations in (a) characterizing brain development (most studies were based on subjective tools such as questionnaires or neuropsychological tests) and (b) air pollution exposure (most studies only used residential levels based on geographical modelling and also overlooking the variation in the mixture of air pollutants as well as the composition and hence toxicity of particulate pollutants in different settings), (c) the lack of studies during the most vulnerable stages of brain development (foetal and early life (first two years post‐natally)) and (d) the lack of structural and functional imaging data underlying these effects. In mice, in utero exposure to fine particles was linked to structural brain changes and there is a need to establish the generalizability of these findings in human beings. Though scarce, current evidence in children supports the importance of the pre‐natal period as a susceptible window of exposure. Two studies in schoolchildren found that pre‐natal air pollution exposure might damage brain structure while exposure during childhood was not linked to any structural alteration. Another study showed that children with higher traffic‐related air pollution at school had lower functional integration in key brain networks, but no changes in brain structure, possibly partly because of the time window of air pollution exposure (in utero versus childhood exposure). A key development is to discover the windows of greatest sensitivity of structural brain changes to air pollution exposure by incorporating the recent advances in non‐invasive imaging to characterize natal and post‐natal brain development and exploring whether and to what extend placental dysfunction could mediate such an association. Studying pre‐natal life is important because effects at this time are of a potentially irreversible nature and because the largest preventive opportunities occur during these periods.

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“…There were fractional anisotropy changes in multiple regions of the brain in 1 day‐old kits in response to uteroplacental insufficiency (Eixarch et al, ). Moreover, rabbits exposed to uteroplacental insufficiency displayed neurobehavioral alterations such as reduced exploratory activities/increased anxiety‐related behavior as adults (Batalle et al, ; Illa et al, ). The findings of impaired neurocognitive development and function in rabbit kits were in line with those of rat offspring that showed altered spatial memory, motor function, and sensorimotor gating function as a result of uteroplacental insufficiency during development (Lauritz, Siebel, Guille, Jefferies, & Wlodek, ).…”

Section: Models Of Iugr and Fetal Programmingmentioning

confidence: 99%

Models of Intrauterine growth restriction and fetal programming in rabbits

López-Tello

Álvarez

González-Bulnes³

et al. 2019

Molecular Reproduction Devel

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Intrauterine growth restriction (IUGR) affects approximately 10% of human pregnancies globally and has immediate and life‐long consequences for offspring health. However, the mechanisms underlying the pathogenesis of IUGR and its association with later health and disease outcomes are poorly understood. To address these knowledge gaps, the use of experimental animals is critically important. Since the 50's different environmental, pharmacological, and surgical manipulations have been performed in the rabbit to improve our knowledge of the control of fetal growth, fetal responses to IUGR, and mechanisms by which offspring may be programmed by an adverse gestational environment. The purpose of this review is therefore to summarize the utility of the rabbit as a model for IUGR research. It first summarizes the knowledge of prenatal and postnatal development in the rabbit and how these events relate to developmental milestones in humans. It then describes the methods used to induce IUGR in rabbits and the knowledge gained about the mechanisms determining prenatal and postnatal outcomes of the offspring. Finally, it discusses the application of state of the art approaches in the rabbit, including high‐resolution ultrasound, magnetic resonance imaging, and gene targeting, to gain a deeper integrative understanding of the physiological and molecular events governing the development of IUGR. Overall, we hope to engage and inspire investigators to employ the rabbit as a model organism when studying pregnancy physiology so that we may advance our understanding of mechanisms underlying IUGR and its consequences in humans and other mammalian species.

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Neurodevelopmental Effects of Undernutrition and Placental Underperfusion in Fetal Growth Restriction Rabbit Models

Cited by 18 publications

References 39 publications

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

Pre‐natal brain development as a target for urban air pollution

Models of Intrauterine growth restriction and fetal programming in rabbits

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