A neonatal piglet model for investigating brain and cognitive development in small for gestational age human infants.

A neonatal piglet model for investigating brain and cognitive development in small for gestational age human infants.
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DOI:
10.1371/journal.pone.0091951
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Johnson RW
Johnson RW
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Radlowski EC;Conrad MS;Lezmi S;Dilger RN;Sutton B;Larsen R;Johnson RW

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研究了仔猪作为研究与出生小于胎龄(SGA)相关的脑和认知缺陷的潜在模型。在出生后第2天(PD)获得自然分娩的SGA(0.7-1.0 kg BW)和平均胎龄(阿加,1.3-1.6 kg BW)仔猪,置于单独的笼中,并提供营养充足的牛奶添加剂饮食(285 ml/kg/d)。从PD 14开始,评估空间T迷宫任务中的表现。在PD 28时,麻醉仔猪进行磁共振(MR)成像,以评估大脑结构(基于体素的形态测定)、连接性(扩散张量成像)以及海马和胼胝体中的代谢物(质子MR波谱)。SGA仔猪表现出补偿性生长,到PD 15时,SGA和阿加仔猪的体重相似(P>0.05)。出生体重影响迷宫性能,SGA仔猪比阿加仔猪需要更长的时间达到标准(p<0.01)。SGA和阿加仔猪的总脑体积相似(P<0.05),但总体而言,SGA仔猪的灰质少于阿加仔猪(p<0.01),并且倾向于具有较小的内囊(p = 0.07)。  SGA和阿加仔猪之间的组比较定义了9个区域(≥ 20簇),其中SGA仔猪具有较少的白色物质(p<0.01); 2个区域,其中SGA仔猪具有较多的白色物质(p<0.01); 3个区域,其中SGA仔猪具有较多的灰质(p<0.01)。出生SGA对白色物质的影响得到了SGA仔猪较低(p<0.04)的各向异性分数值的支持,表明白色物质发育和连通性降低。各组间测定的代谢物均无差异。总之,结果表明,SGA仔猪存在空间学习缺陷和白色物质发育异常。由于白色物质中的学习缺陷和异常在SGA人类婴儿中很常见,因此仔猪是一种易于处理的转化模型,可用于研究SGA相关的认知缺陷和潜在的干预措施。
The piglet was investigated as a potential model for studying brain and cognitive deficits associated with being born small for gestational age (SGA). Naturally farrowed SGA (0.7–1.0 kg BW) and average for gestational age (AGA, 1.3–1.6 kg BW) piglets were obtained on postnatal day (PD) 2, placed in individual cages, and provided a nutritionally adequate milk replacer diet (285 ml/kg/d). Beginning at PD14, performance in a spatial T-maze task was assessed. At PD28, piglets were anesthetized for magnetic resonance (MR) imaging to assess brain structure (voxel-based morphometry), connectivity (diffusion-tensor imaging) and metabolites in the hippocampus and corpus callosum (proton MR spectroscopy). Piglets born SGA showed compensatory growth such that BW of SGA and AGA piglets was similar (P>0.05), by PD15. Birth weight affected maze performance, with SGA piglets taking longer to reach criterion than AGA piglets (p<0.01). Total brain volume of SGA and AGA piglets was similar (P<0.05), but overall, SGA piglets had less gray matter than AGA piglets (p<0.01) and tended to have a smaller internal capsule (p = 0.07). Group comparisons between SGA and AGA piglets defined 9 areas (≥ 20 clusters) where SGA piglets had less white matter (p<0.01); 2 areas where SGA piglets had more white matter (p<0.01); and 3 areas where SGA piglets had more gray matter (p<0.01). The impact of being born SGA on white matter was supported by a lower (p<0.04) fractional anisotropy value for SGA piglets, suggesting reduced white matter development and connectivity. None of the metabolites measured were different between groups. Collectively, the results show that SGA piglets have spatial learning deficits and abnormal development of white matter. As learning deficits and abnormalities in white matter are common in SGA human infants, the piglet is a tractable translational model that can be used to investigate SGA-associated cognitive deficits and potential interventions.
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