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Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model.

ABSTRACT: Preterm birth is the most significant problem in contemporary obstetrics accounting for 5-18% of worldwide deliveries. Encephalopathy of prematurity encompasses the multifaceted diffuse brain injury resulting from preterm birth. Current animal models exploring the underlying pathophysiology of encephalopathy of prematurity employ significant insults to generate gross central nervous system abnormalities. To date the exclusive effect of prematurity was only studied in a non-human primate model. Therefore, we aimed to develop a representative encephalopathy of prematurity small animal model only dependent on preterm birth. Time mated New-Zealand white rabbit does were either delivered on 28 (pre-term) or 31 (term) postconceptional days by caesarean section. Neonatal rabbits underwent neurobehavioral evaluation on 32 days post conception and then were transcardially perfuse fixed. Neuropathological assessments for neuron and oligodendrocyte quantification, astrogliosis, apoptosis and cellular proliferation were performed. Lastly, ex-vivo high-resolution Magnetic Resonance Imaging was used to calculate T1 volumetric and Diffusion Tensor Imaging derived fractional anisotropy and mean diffusivity. Preterm birth was associated with a motoric (posture instability, abnormal gait and decreased locomotion) and partial sensory (less pain responsiveness and failing righting reflex) deficits that coincided with global lower neuron densities, less oligodendrocyte precursors, increased apoptosis and less proliferation. These region-specific histological changes corresponded with Magnetic Resonance Diffusion Tensor Imaging differences. The most significant differences were seen in the hippocampus, caudate nucleus and thalamus of the preterm rabbits. In conclusion this model of preterm birth, in the absence of any other contributory events, resulted in measurable neurobehavioral deficits with associated brain structural and Magnetic Resonance Diffusion Tensor Imaging findings.

SUBMITTER: van der Merwe J

PROVIDER: S-EPMC6401068 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model.

van der Merwe Johannes J van der Veeken Lennart L Ferraris Sebastiano S Gsell Willy W Himmelreich Uwe U Toelen Jaan J Ourselin Sebastien S Melbourne Andrew A Vercauteren Tom T Deprest Jan J

Scientific reports 20190305 1

Preterm birth is the most significant problem in contemporary obstetrics accounting for 5-18% of worldwide deliveries. Encephalopathy of prematurity encompasses the multifaceted diffuse brain injury resulting from preterm birth. Current animal models exploring the underlying pathophysiology of encephalopathy of prematurity employ significant insults to generate gross central nervous system abnormalities. To date the exclusive effect of prematurity was only studied in a non-human primate model. T ...[more]

PMID: 30837582

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Project description:Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions.To characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth.This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term.A total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within-subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth.In a predominantly African-American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.

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Dataset Information

Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model.

Publications

Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model.

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