There is an ongoing need for relevant animal models in which to test therapeutic interventions for infants with neurological sequelae of prematurity. The ferret is an attractive model species as it has a gyrified brain with a white-to-gray matter ratio similar to that in the human brain. A model of encephalopathy of prematurity was developed in postnatal day 10 (P10) ferret kits, considered to be developmentally equivalent to infants of 24-26 weeks' gestation. Cross-fostered P10 ferret kits received 5 mg/kg of lipopolysaccharide (LPS) before undergoing consecutive hypoxia-hyperoxia-hypoxia (60 min at 9%, 120 min at 60%, and 30 min at 9%). Control animals received saline vehicle followed by normoxia. The development of basic reflexes (negative geotaxis, cliff aversion, and righting) as well as gait coordination on an automated catwalk were assessed between P28 and P70, followed by ex vivo magnetic resonance imaging (MRI) and immunohistochemical analysis. Compared to controls, injured animals had slower overall reflex development between P28 and P40, as well as smaller hind-paw areas consistent with "toe walking" at P42. Injured animals also displayed significantly greater lateral movement during CatWalk assessment as a result of reduced gait coordination. Ex vivo MRI showed widespread white-matter hyperintensity on T2-weighted imaging as well as altered connectivity patterns. This coincided with white-matter dysmaturation characterized by increased intensity of myelin basic protein staining, white-matter thinning, and loss of oligodendrocyte transcription factor 2 (OLIG2)-positive cells. These results suggest both pathological and motor deficits consistent with premature white-matter injury. This newborn ferret model can therefore provide an additional platform to assess potential therapies before translation to human clinical trials.

中文翻译：

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早产儿脑病的雪貂模型。

一直需要相关的动物模型来测试患有早产儿神经系统后遗症的婴儿的治疗干预措施。雪貂是一种有吸引力的模型物种，因为它具有回旋的大脑，白灰比与人脑相似。在出生后第10天（P10）的雪貂套件中开发了早产儿脑病模型，该套件被认为在发育上等同于妊娠24-26周的婴儿。交叉培养的P10雪貂试剂盒接受5 mg / kg的脂多糖（LPS），然后连续进行低氧-高氧-低氧（9％为60分钟，60％为120分钟，9％为30分钟）。对照动物接受盐溶媒，然后进行常氧。基本反射的发展（负地轴，悬崖避险，在P28和P70之间评估自动走道上的步态和步态协调性，然后进行离体磁共振成像（MRI）和免疫组织化学分析。与对照组相比，受伤的动物在P28和P40之间的整体反射发育较慢，并且后爪区域较小，与P42处的“脚趾行走”一致。由于步态协调性降低，在CatWalk评估中受伤的动物还表现出明显更大的横向运动。体外MRI在T2加权成像上显示广泛的白质高信号以及改变的连接方式。这与白质失调同时发生，其特征在于髓鞘碱性蛋白染色强度增加，白质变薄以及少突胶质细胞转录因子2（OLIG2）阳性细胞的丢失。这些结果表明病理和运动功能障碍均与过早的白质损伤相一致。因此，这种新生的雪貂模型可以提供一个额外的平台，以便在翻译为人类临床试验之前评估潜在的疗法。