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

Illa, M.; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz‐Moreno, Emma; Crispi, F.; Udina, Esther; Figueras, F.; Ginés, Sílvia; Gratacós, E.

doi:10.1159/000481171

Cited by 16 publications

(20 citation statements)

References 53 publications

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“…Analysis of the neonatal rat brain using a combination of advanced MRI analysis and histology demonstrates that gray and white matter microstructure is normalized with lactoferrin supplementation, myelination is protected and measures of axonal integrity and brain organization are restored in rats with lactoferrin supplementation (201). Early environment enrichment or postnatal stimulation has also been shown to have some benefits in brain connectivity in a rabbit model of FGR (203). While there are no current published studies on stem cell therapy for FGR related brain injury, our lab and others are working on testing their applications in FGR and other pregnancy complications (204).…”

Section: Specific Neonatal Morbidities (Table 1)mentioning

confidence: 99%

Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact

et al. 2019

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Being born small lays the foundation for short-term and long-term implications for life. Intrauterine or fetal growth restriction describes the pregnancy complication of pathological reduced fetal growth, leading to significant perinatal mortality and morbidity, and subsequent long-term deficits. Placental insufficiency is the principal cause of FGR, which in turn underlies a chronic undersupply of oxygen and nutrients to the fetus. The neonatal morbidities associated with FGR depend on the timing of onset of placental dysfunction and growth restriction, its severity, and the gestation at birth of the infant. In this review, we explore the pathophysiological mechanisms involved in the development of major neonatal morbidities in FGR, and their impact on the health of the infant. Fetal cardiovascular adaptation and altered organ development during gestation are principal contributors to postnatal consequences of FGR. Clinical presentation, diagnostic tools and management strategies of neonatal morbidities are presented. We also present information on the current status of targeted therapies. A better understanding of neonatal morbidities associated with FGR will enable early neonatal detection, monitoring and management of potential adverse outcomes in the newborn period and beyond.

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Section: Specific Neonatal Morbidities (Table 1)mentioning

confidence: 99%

Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact

et al. 2019

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“…A study in FGR (small for gestational age infants) and AGA neonates showed lower FA and higher diffusivity (AD, MD, RD) in FGR infants as compared to AGA infants in a number of brain regions out of a total of 122 brain regions studied (Wang et al, 2017). Similarly, a study in FGR rabbits also showed altered brain networks and decreased FA in the hippocampus (Illa et al, 2018). We did not observe any changes in DTI measures in the six brain regions studied within the FGR lamb brain.…”

Section: Discussionmentioning

confidence: 90%

Advanced MRI analysis to detect white matter brain injury in growth restricted newborn lambs

Malhotra

Sepehrizadeh

Dhollander

et al. 2019

NeuroImage: Clinical

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Background Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not sensitive enough to detect subtle structural abnormalities in the FGR brain. We examined whether advanced MRI analysis techniques have the capacity to detect brain injury (particularly white matter injury) caused by chronic hypoxia-induced fetal growth restriction in newborn preterm lambs. Methods Surgery was undertaken in twin bearing pregnant ewes at 88–90 days gestation (term = 150 days) to induce FGR in one fetus. At 127 days gestation (~32 weeks human brain development), FGR and control (appropriate for gestational age, AGA) lambs were delivered by caesarean section, intubated and ventilated. Conventional and advanced brain imaging was conducted within the first two hours of life using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) structural imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis of dMRI data included the following regions of interest (ROIs): subcortical white matter, periventricular white matter, cerebellum, hippocampus, corpus callosum and thalamus. Fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of the dMRI data was performed and compared between FGR and AGA lambs. Lambs were euthanised immediately after the scans and brain histology performed in the regions of interest to correlate with imaging. Results FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p = .002) MRI brain scans were analysed. There were no statistically significant differences observed between the groups in conventional T1w, T2w or MRS brain data. Mean, axial and radial diffusivity, and fractional anisotropy indices obtained from DTI modelling also did not show any statistically significant differences between groups in the ROIs. Fixel-based analysis of 3-tissue CSD, however, did reveal a decrease in fibre cross-section (FC, p < .05) but not in fibre density (FD) or combined fibre density and cross-section (FDC) in FGR vs. AGA lamb brains. The specific tracts that showed a decrease in FC were in the regions of the periventricular white matter, hippocampus and cerebellar white matter, and were supported by histological evidence of white matter hypomyelination and disorganisation in corresponding FGR lamb brain regions. Conclusions The neuropathology associated with FGR in neonatal preterm lambs is subtle and imaging detection may require advanced MRI and tract-based analysis techniques. Fixel-based analysis of 3-tissue CSD demonstrates that the preterm neonatal FGR brain shows evidence of macrostructural (cross-sectional) deficits in white matter subsequent to altered antenat...

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“…An analysis performed for a subgroup of fetuses that weighed less than 30 grams (which correspond to the 10 th centile of normally distributed weight at birth [ 3 , 6 , 34 – 36 ]) revealed that a significantly higher proportion of IUGR-T animals with that weight were alive compared to IUGR animals ( Fig 2B ).…”

Section: Resultsmentioning

confidence: 99%

Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

et al. 2018

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ObjectiveTo evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR).MethodsIUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40–50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight.ResultsSurvival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups.ConclusionIntra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency.

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

Cited by 16 publications

References 53 publications

Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact

Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact

Advanced MRI analysis to detect white matter brain injury in growth restricted newborn lambs

Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

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