Lee Minyoung, Kim Eun-Jin, Woo Dong-Cheol, Shim Woo-Hyun, Yum Mi-Sun
Department of Pediatrics, Asan Medical Center, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South Korea.
Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
Front Neurosci. 2020 May 20;14:510. doi: 10.3389/fnins.2020.00510. eCollection 2020.
Malformations of cortical development (MCDs) are major causes of intractable epilepsies. To characterize the early neuroimaging findings of MCDs, we tried to identify the MRI features consistent with pathological findings in an infant rat MCD model, prenatally exposed to methylazoxymethanol (MAM), by using newly developed MRI techniques. At gestational day 15, two doses of MAM (15 mg/kg intraperitoneally) or normal saline were injected into pregnant rats. The offspring underwent MRI, including glutamate chemical exchange saturation transfer (GluCEST), H-MR spectroscopy, and diffusion tensor imaging, at postnatal day (P) 15 using a 7T small-animal imaging system. Another set of prenatally MAM-exposed rats were sacrificed for histological staining. At P15, the retrosplenial cortex (RSC) of rats with MCDs showed decreased neuronal nuclei, parvalbumin, and reelin expressions. Moreover, dendritic arborization of pyramidal cells in the RSC significantly decreased in infant rats with MCDs. MRI showed significantly decreased GluCEST (%) in the RSC of rats with MCDs ( = 0.000) and a significant correlation between GluCEST (%) and RSC thickness ( = 0.685, = 0.003). The rats with MCDs showed reduced glutamate ( = 0.002), -acetylaspartate ( = 0.002), and macromolecule and lipid levels ( = 0.027) and significantly reduced fractional anisotropy values in the RSC. MRI revealed reduced neuronal population and dendritic arborization in the RSC of infant rats with MCDs during the early postnatal period. These pathological changes of the cortex could serve as clinical imaging biomarkers of MCDs in infants.
皮质发育畸形（MCDs）是难治性癫痫的主要病因。为了描述MCDs的早期神经影像学表现，我们试图通过使用新开发的MRI技术，在产前暴露于甲基偶氮甲醇（MAM）的幼鼠MCD模型中识别与病理结果一致的MRI特征。在妊娠第15天，向怀孕大鼠腹腔注射两剂MAM（15 mg/kg）或生理盐水。在出生后第15天（P15），使用7T小动物成像系统对后代进行MRI检查，包括谷氨酸化学交换饱和转移（GluCEST）、氢磁共振波谱和扩散张量成像。另一组产前暴露于MAM的大鼠被处死用于组织学染色。在P15时，患有MCDs的大鼠的压后皮质（RSC）显示神经元细胞核、小白蛋白和Reelin表达减少。此外，患有MCDs的幼鼠RSC中锥体细胞的树突分支明显减少。MRI显示，患有MCDs的大鼠RSC中的GluCEST（%）显著降低（P = 0.000），并且GluCEST（%）与RSC厚度之间存在显著相关性（r = 0.685，P = 0.003）。患有MCDs的大鼠RSC中的谷氨酸（P = 0.002）、N-乙酰天门冬氨酸（P = 0.002）以及大分子和脂质水平（P = 0.027）降低，并且RSC中的各向异性分数值显著降低。MRI显示，患有MCDs的幼鼠在出生后早期RSC中的神经元数量和树突分支减少。皮质的这些病理变化可作为婴儿MCDs的临床影像学生物标志物。
