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脑损伤的仔猪:胎儿生长受限的转化模型。

Brain Outcomes in Runted Piglets: A Translational Model of Fetal Growth Restriction.

机构信息

UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

The Australian E-Health Research Centre, CSIRO, Brisbane, Queensland, Australia.

出版信息

Dev Neurosci. 2022;44(4-5):194-204. doi: 10.1159/000523995. Epub 2022 Mar 9.

Abstract

Fetal growth restriction (FGR) is associated with long-term neurodevelopmental disabilities including learning and behavioral disorders, autism, and cerebral palsy. Persistent changes in brain structure and function that are associated with developmental disabilities are demonstrated in FGR neonates. However, the mechanisms underlying these changes remain to be determined. There are currently no therapeutic interventions available to protect the FGR newborn brain. With the wide range of long-term neurodevelopmental disorders associated with FGR, the use of an animal model appropriate to investigating mechanisms of injury in the FGR newborn is crucial for the development of effective and targeted therapies for babies. Piglets are ideal animals to explore how perinatal insults affect brain structure and function. FGR occurs spontaneously in the piglet, unlike other animal models that require surgical or chemical intervention, allowing brain outcomes to be studied without the confounding impacts of experimental interventions. The FGR piglet mimics many of the human pathophysiological outcomes associated with FGR including asymmetrical growth restriction with brain sparing. This review will discuss the similarities observed in brain outcomes between the FGR human and FGR piglet from a magnetic resonance imaging in the living and a histological perspective. FGR piglet studies provide the opportunity to determine and track mechanisms of brain injury in a clinically relevant animal model of FGR. Findings from these FGR piglet studies may provide critical information to rapidly translate neuroprotective interventions to clinic to improve outcomes for newborn babies.

摘要

胎儿生长受限(FGR)与长期神经发育障碍有关,包括学习和行为障碍、自闭症和脑瘫。在 FGR 新生儿中,与发育障碍相关的大脑结构和功能的持续变化得到了证实。然而,这些变化的机制仍有待确定。目前尚无治疗干预措施可保护 FGR 新生儿的大脑。由于与 FGR 相关的长期神经发育障碍范围广泛,使用适合研究 FGR 新生儿损伤机制的动物模型对于开发针对婴儿的有效和有针对性的治疗方法至关重要。仔猪是探索围产期损伤如何影响大脑结构和功能的理想动物。与其他需要手术或化学干预的动物模型不同,FGR 会在仔猪中自发发生,因此可以在没有实验干预混杂影响的情况下研究大脑结果。FGR 仔猪模拟了许多与 FGR 相关的人类病理生理学结果,包括大脑保留的不对称生长受限。这篇综述将从活体磁共振成像和组织学的角度讨论 FGR 人类和 FGR 仔猪之间在大脑结果方面观察到的相似性。FGR 仔猪研究为在临床相关的 FGR 动物模型中确定和跟踪脑损伤机制提供了机会。这些 FGR 仔猪研究的结果可能为迅速将神经保护干预措施转化为临床提供关键信息,以改善新生儿的结局。

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