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早期环境富集改善宫内生长受限兔模型的异常脑连接

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

作者信息

Illa Miriam, Brito Verónica, Pla Laura, Eixarch Elisenda, Arbat-Plana Ariadna, Batallé Dafnis, Muñoz-Moreno Emma, Crispi Fatima, Udina Esther, Figueras Francesc, Ginés Silvia, Gratacós Eduard

机构信息

Fetal i+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia, Obstetricia i Neonatologia, Universitat de Barcelona, Barcelona, Spain.

出版信息

Fetal Diagn Ther. 2018;44(3):184-193. doi: 10.1159/000481171. Epub 2017 Oct 12.

Abstract

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.

摘要

引言

与宫内生长受限(IUGR)相关的神经发育障碍在生命后期持续存在的结构对应关系仍不清楚。此外,已提出产后早期刺激策略来减轻这些影响。本研究探讨了IUGR兔模型中的长期脑连接异常以及产后早期环境富集(EE)的影响。

材料与方法

通过手术在一侧子宫角诱导IUGR,而对侧作为对照。产后,将IUGR动物的一个亚组置于富集环境中。在新生儿期和长期进行功能评估。在长期阶段,通过扩散加权脑磁共振成像和聚焦于海马体的组织学评估来评价脑结构连接性。

结果

IUGR动物的功能结果较差,全脑网络改变,海马体中的平均各向异性分数降低。还观察到海马神经元的树突棘和神经元周围网络密度降低。值得注意的是,暴露于富集环境的IUGR动物在功能和结构方面均有改善。

结论

IUGR与全球和细胞水平上的脑连接改变有关。基于早期EE的策略有可能恢复IUGR的神经发育后果。

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