Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU Leuven University of Leuven, Leuven, Belgium.
Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospitals Leuven, Leuven, Belgium.
Sci Rep. 2019 Mar 5;9(1):3506. doi: 10.1038/s41598-019-39922-8.
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.
早产是当代产科中最重大的问题，占全球分娩的 5-18%。早产儿脑病包括由早产引起的多方面弥漫性脑损伤。目前探索早产儿脑病潜在病理生理学的动物模型采用了重大损伤来产生明显的中枢神经系统异常。迄今为止，仅在非人类灵长类动物模型中研究了早产的排他性影响。因此，我们旨在开发一种仅依赖早产的代表性早产儿脑病小动物模型。时间交配的新西兰白兔母兔通过剖腹产分娩在 28 天（早产）或 31 天（足月）。新生兔在妊娠后 32 天接受神经行为评估，然后进行心脏灌注固定。进行神经元和少突胶质细胞数量、星形胶质细胞增生、细胞凋亡和细胞增殖的神经病理学评估。最后，进行离体高分辨率磁共振成像以计算 T1 容积和扩散张量成像得出的各向异性分数和平均扩散率。早产与运动（姿势不稳定、异常步态和运动减少）和部分感觉（疼痛反应性降低和翻正反射失败）缺陷有关，这与神经元密度普遍降低、少突胶质细胞前体减少、凋亡增加和增殖减少有关。这些特定区域的组织学变化与磁共振扩散张量成像的差异相对应。在早产兔中，最显著的差异见于海马体、尾状核和丘脑。总之，这种没有任何其他促成事件的早产模型导致了可测量的神经行为缺陷，以及相关的大脑结构和磁共振扩散张量成像发现。
